Feedback controlled sacral nerve stimulation for treating inflammatory bowel disease

Abstract

Systems and methods for controlling sacral nerve stimulation for treating Inflammatory Bowel Disease (IBD) using measured physiologic parameters are described herein. For example, measurement of physiologic parameters can be obtained via a swallowable capsule, implant, or wearable device, and can be used to adjust stimulation parameters. The physiologic measurement data can also be collected over time to build a predictive model that can be used to pre-emptively provide therapy, and / or can be used to screen a plurality of candidate stimulation programs.

Description

FEEDBACK CONTROLLED SACRAL NERVE STIMULATION FOR TREATING INFLAMMATORY BOWEL DISEASECROSS-REFERENCE TO RELATED APPLICATION(S)

[0001] The present application claims priority to U.S. Provisional Patent Application No. 63 / 651 ,907, filed May 24, 2024, the disclosure of which is incorporated by reference herein in its entirety.TECHNICAL FIELD

[0002] The present technology is directed toward electrically modulating nervous tissue to treat a patient condition.BACKGROUND

[0003] Inflammatory Bowel Disease (IBD) is a digestive disorder characterized by chronic inflammation of the gastrointestinal tract. IBD includes both Crohn’s disease, which causes intermittent inflammation of the gastrointestinal tract, and ulcerative colitis, which causes continuous inflammation of the colon. Both Crohn’s disease and ulcerative colitis cause similar patient symptoms, including patient discomfort (e.g., abdominal pain), abnormal gastrointestinal tract function (e.g., diarrhea, bowel urgency, bowel frequency, and fecal incontinence), and other complications (e.g., fever, weight loss, etc.). IBD is typically treated using pharmaceutical therapies including antiinflammatory drugs and immune system suppressors. In extreme cases, patients may even undergo surgery to remove inflamed or damaged portions of the colon or other portions of the digestive tract. However, neither pharmaceuticals nor surgery cure IBD, and symptoms often persist or recur during or after treatment. Moreover, in certain patients, pharmaceuticals and surgery have minimal efficacy and / or induce unwanted side effects. Accordingly, a need exists for improved treatments for IBD.

[0004] Neurological stimulation systems generally have a signal generator that generates electrical pulses, and one or more signal delivery devices such as leads that deliver the electrical pulses to neurological tissue or muscle tissue. The delivered electrical pulses modulate neural activity to treat an underlying patient condition. For example, neurostimulation has been used to treat various disorders such as pain,movement disorders, cardiac disorders, and various other medical conditions. Sacral neuromodulation (SNM) is a type of neuromodulation in which electrical stimulation is applied to one or more sacral nerves to treat a patient condition. SNM has been used to treat various urological disorders, including urinary retention, urinary urge incontinence, urgency frequency, and fecal incontinence.BRIEF DESCRIPTION OF THE DRAWINGS

[0005] Figure 1 is a partially schematic illustration of an implantable sacral neuromodulation system positioned at a patient’s sacral region to deliver electrical signals in accordance with some embodiments of the present technology.

[0006] Figure 1 B is another partially schematic illustration of the system of Figure 1 A.

[0007] Figure 1 C illustrates sacral nerve anatomy of a patient, along with a portion of a signal delivery device of the system of Figure 1 A shown as implanted at a representative location in accordance with some embodiments of the present technology.

[0008] Figure 2A is a partially schematic illustration of an electrical signal generated in accordance with some embodiments of the present technology.

[0009] Figure 2B is a partially schematic illustration of another electrical signal generated in accordance with some embodiments of the present technology.

[0010] Figure 3 is a flowchart of an example method of controlling sacral nerve stimulation in a patient based at least in part on one or more sensed physiological parameters and in accordance with some embodiments of the present technology.

[0011] Figure 4 is a flowchart of an example method of controlling sacral nerve stimulation in a patient using a predictive model in accordance with some embodiments of the present technology.

[0012] Figure 5 is a flowchart of an example method of identifying a stimulation program out of a plurality of candidate treatment programs for sacral nerve stimulation in a patient in accordance with some embodiments of the present technology.DETAILED DESCRIPTIONA. Introduction

[0013] The present technology is directed to systems and methods for controlling sacral nerve stimulation for treating Inflammatory Bowel Disease (IBD) by measuring one or more physiologic parameters of a patient. As described throughout this Detailed Description, the measured physiologic parameters can be analyzed to initiate stimulation therapy, cease stimulation therapy, and / or adjust one or more signal delivery parameters for the therapy. Such therapy parameters that can be adjusted based on the measured physiologic parameters include, but are not limited to, amplitude, frequency, pulse width, duty cycle, electrode combination, and stimulation session length. In some embodiments, the measured physiologic parameters can be used to generate and / or update a predictive model that can be used to (a) predict when symptomatic episodes may occur in a patient, and (b) identify stimulation parameters that are expected to be effective in treating and / or preventing the symptomatic episode. In yet other embodiments, the measured physiologic parameters can be used to screen a plurality of candidate stimulation programs, e.g., to identify which of the candidate stimulation programs may be most effective for a particular patient.

[0014] Unless otherwise stated, the terms “generally,” “about,” and “approximately” refer to values within 10% of a stated value. For example, the use of the term “about 100” refers to a range of 90 to 110, inclusive. In instances in which relative terminology is used in reference to something that does not include a numerical value, the terms are given their ordinary meaning to one skilled in the art.

[0015] As used herein, and unless otherwise noted, the terms “modulate,” “modulation,” “stimulate,” and “stimulation” refer generally to electrical signals that have an inhibitory, excitatory, and / or other effect on a target neural population. Accordingly, a sacral nerve “stimulator” can have an inhibitory effect and / or an excitatory effect on certain neural populations.

[0016] As used herein, the terms “electrical therapy signal,” “electrical signal,” “therapy signal,” “signal,” and other associated terms are used interchangeably and generally refer to an electrical signal that can be characterized by one or more parameters, such as frequency, pulse width, and / or amplitude.

[0017] As used herein, “proximate a target neural population” refers to the placement of a signal delivery element such that it can deliver electrical stimulation to the target neural population. For example, if the target population includes the third sacral spinal nerve, “proximate the target neural population” includes, but is not limited to, the relative lead positions described and shown in Figure 1 C, as well as other positions not expressly described herein.

[0018] Specific details of certain embodiments of the disclosure are described below with reference to methods for modulating one or more target neural populations (e.g., nerves) or sites of a patient, and associated implantable structures for providing the modulation. Although selected embodiments are described below with reference to modulating the sacral nerves, the modulation may in some instances be directed to other neurological structures and / or target neural populations and / or other neurological tissues throughout the body. For example, some embodiments may include modulating the vagus nerve, the splenic nerve, the splanchnic nerve, and / or other peripheral nerves. Some embodiments can have configurations, components, and / or procedures different than those described herein, and other embodiments may eliminate particular components and / or procedures. A person of ordinary skill in the relevant art, therefore, will understand that the present disclosure may include other embodiments with additional elements, and / or may include other embodiments without several of the features shown and described below with reference to Figures 1 A-5.B. Representative Embodiments of Sacral Neuromodulation Systems and Associated Stimulation Waveforms

[0019] Figure 1A schematically illustrates a sacral neuromodulation system 100 (“the system 100”) implanted to stimulate a patient’s sacral nerves and configured in accordance with embodiments of the present technology. The system 100 includes a signal generator 1 10 and a signal delivery device 120. The signal generator 110 can be implanted and / or implantable subcutaneously within the patient P. For example, in the illustrated embodiment the signal generator 110 is implanted subcutaneously at the lower back / upper buttock area of the patient P (e.g., adjacent but posterior to the iliac crest IC and / or iliac fossa IF).

[0020] The signal delivery device 120 extends from the signal generator 1 10 and can be implanted within the patient P proximate a target neural population. In someembodiments, the target neural population includes one or more of the sacral spinal nerves (e.g., the S1 sacral nerve, the S2 sacral nerve, the S3 sacral nerve and / or the S4 sacral nerve). Accordingly, in some embodiments the signal delivery device 120 can extend through one of the sacral foramen S1 -S4 (the illustrated embodiment depicts the signal delivery device 120 extending through the sacral foramen S1 ) and adjacent one or more sacral spinal nerves when implanted. More specifically, the signal delivery device 120 can be implanted proximate the S1 sacral nerve, the S2 sacral nerve, the S3 sacral nerve, and / or the S4 sacral nerve. The signal delivery device 120 can carry features configured to administer therapy to the target neural population. For example, the signal delivery device 120 can include one or more lead(s) or lead bodies 122 extending from the signal generator 110 toward the target neural population (e.g., toward the S3 sacral nerve). As described in greater detail with reference to Figure 1 C, the lead 122 can include or carry one or more electrical contacts or electrodes (e.g., ring electrodes, cuff electrodes, and / or other suitable electrical contacts) that deliver electrical signals to the target neural population.

[0021] In operation, the signal generator 1 10 can generate and transmit signals (e.g., electrical signals) to the signal delivery device 120. In turn, the signal delivery device 120 can deliver the electrical signals to the target neural population, e.g., to electrically modulate neurons within the target neural population to induce a therapeutic effect in the patient. Representative electrical signals that can be generated by the signal generator 1 10 and delivered to the patient P via the signal delivery device 120 are described in greater detail below with reference to Figures 2A and 2B.

[0022] The signal generator 110 can include a machine-readable (e.g., computer- readable) medium containing instructions for generating and transmitting electrical signals. Accordingly, generating electrical signals in accordance with the methods described herein can include executing computer-executable instructions contained by, on, or in computer-readable media located within the signal generator 1 10. The signal generator 110 can also include one or more processors for executing the machine- readable instructions, memory unit(s), batteries (rechargeable and / or non- rechargeable), communication devices (e.g., an antenna), and / or other software or hardware-based components. As shown in Figure 1 A, the signal generator 1 10 can include a single housing for storing some or all of the foregoing components, althoughin other embodiments some or all of the foregoing components can be stored in separate housings.

[0023] In some embodiments, the signal generator 1 10 can be configured to communicate with one or more external controllers or computing systems 104. For example, the signal generator 1 10 can wirelessly communicate with a physician controller that is external to the patient P. In some embodiments, the physician controller can include a software and / or firmware module stored at least partially on the computing system 104. A physician or other healthcare provider can therefore use the physician controller to program the signal generator 1 10, e.g., to select parameters for the electrical signal to be generated by the signal generator 110. In some embodiments, the signal generator 110 can also communicate with a patient controller (not shown) that is external to the patient P. The patient P can use the patient controller to control various aspects of the therapy provided by the signal generator 110. For example, the patient may be able to start and stop electrical stimulation therapy using the patient controller, and / or control certain parameters (e.g., amplitude) of the electrical stimulation using the patient controller. In some embodiments, the signal generator 110 can transmit data to the external controller 104 (e.g., to the physician controller and / or the patient controller) for user review. For example, the signal generator 110 may periodically (or on demand) transmit data associated with one or more of electrode impedance, battery power, program settings (e.g., current signal parameters), historical program settings (e.g., historical signal parameters), program / parameter changes, usage data (e.g., stimulation start and stop times), or the like. The physician controller and the patient controller can include a dedicated controller device, or be implemented as an application on a smartphone, tablet, etc.

[0024] In some embodiments, the system 100 can include one or more sensors configured to measure one or more physiological parameters of the patient P. In some embodiments, the one or more sensors include a first sensor 1 15a that is coupled to or contained within the signal generator 1 10. In other embodiments, the one or more sensors include a second sensor 115b that is configured to be implanted within the patient but is not physically coupled to or a part of the signal generator 110. In yet other embodiments, the one or more sensors include a third sensor 115c that is configured to remain external to the patient, e.g., as a wearable device. The sensors 1 15a-c can measure one or more physiologic parameters associated with the patient (which canalso be referred to as “physiological measurement data”). For example, the sensors 115a-c can measure various physiologic metrics including, but not limited to, heart rate, heart rate variability, body temperature, body position, body movement, electrical signals (e.g., neural activity from muscles or nerves), peristaltic activity of the gut, gut evacuation via bowel movements, gut motility, internal organ sounds, electrical impedance between tissues, respiratory rate, blood oxygen level, various biomarker concentrations (e.g., cytokines, chemokines, or other molecules), and the like. Accordingly, the sensors 1 15a-c can include a camera, a microphone, a pH sensor, a biomarker sensor, an electrical activity sensor, an accelerometer, an inclinometer, or other suitable sensors for measuring any of the foregoing parameters.

[0025] The sensors 115a-c can periodically transmit measured physiologic data to the external controller 104 or another computing system, represented by the broken lines in Figure 1 A. Depending on the sensor, this can be done via a wireless (e.g., Bluetooth, RF, NFC, etc.) or wired connection. As described in detail below, the external controller 104 or other computing system can display measured physiologic data, store measured physiologic data, determine trends from measured physiologic data, recommend treatment parameters based on measured physiologic data, or the like. In some embodiments, the sensors 1 15a-c directly transmit data to the signal generator 110 itself, in addition to or in lieu of transmitting data to the external controller 104.

[0026] Although the sensors 115a-c are typically “fixed” to a particular location on and / or within the patient P (e.g., the sensors 115a-c do not move relative to the patient), the system 100 and / or the sensors 1 15a-c can include features that may enable the system to identify a particular location of the data they are measuring. For example, different portions of the gut or different types of activities in the same portion of the gut have different frequency ranges of peristaltic waves. Accordingly, the system 100 can determine the location of measured peristaltic waves by measuring the electrical or acoustic activity of the gut, determining the frequency range of the waves, and comparing the determined frequency range to known frequency ranges for different regions of the gut. In this way, measurements obtained via the sensors 115a-c can be more accurately correlated with specific locations within the patient (e.g., along a specific portion of the patient’s Gl tract).

[0027] In yet other embodiments, the one or more sensors associated with the system 100 can include a sensor carried by a swallowable pill. For example, Figure 1 B illustrates a swallowable pill or capsule 102 having a fourth sensor 115d as it travels through a portion of a gastrointestinal track Gl of the patient P. Similar to the sensors 115a-c, the fourth sensor 115d carried by the capsule 102 is configured to measure, record, and / or transmit one or more physiologic parameters of the patient (which can also be referred to as “physiological measurement data”) as it passes through the patient. Examples of physiologic measurement data that the fourth sensor 1 15d on the capsule 102 can measure, record, and transmit include: (i) the presence or absence of blood in the Gl tract, (ii) the temperature of the Gl tract, (iii) peristaltic wave frequency, strength, and / or timing, (iv) pH of gut contents throughout the Gl tract, (v) gas molecules in the gut, (vi) enzymes and / or cytokines in the gut, (vii) electrical activity of the gut, (viii) sounds within the gut, (ix) gut motility, (x) images of portions of the Gl tract, (xi) videos of portions of the Gl tract, and / or other metrics. Accordingly, the fourth sensor 1 15d can include a camera, a microphone, a pH sensor, a biomarker sensor, an electrical activity sensor, an accelerometer, or other suitable sensors for measuring any of the foregoing parameters.

[0028] In some embodiments the capsule 102 is configured to measure physiologic data from one or more pre-determined portions of the Gl tract. For example, the capsule 102 can be configured to initiate taking physiologic measurements after a pre-determined amount of time has elapsed after the patient P swallowed the capsule (e.g., 1 hour, 2 hours, 3 hours, 4 hours, etc. after the patient P swallowed the capsule). As another example, the capsule 102 can be configured to include a coating (e.g., a biodissolvable coating) that exposes the fourth sensor 1 15d at one or more specific locations within the gut. In yet another example, the position of the capsule 102 within the Gl tract can be monitored using external sensors. When external sensors determine the capsule 102 has reached a specific portion of the Gl tract, the capsule 102 can be triggered to initiate taking physiologic measurements. In this way, the capsule 102 can be used to collect physiological measurement data at specific target regions along the patient’s Gl tract.

[0029] In some embodiments, the capsule 102 is configured to transmit the collected physiological measurement data to the external controller 104 and / or another external data collection system of the system 100. For example, the measurement datacan be transmitted to a computer, mobile device, or electronic database. In some embodiments, the capsule 102 is configured to transmit the physiologic measurement data to the signal controller 110 (shown schematically in Figure 1 B). In yet other embodiments the fourth sensor 115d is configured to measure and record physiologic measurement data, to be collected from the capsule 102 after the capsule 102 has passed through the patient.

[0030] The physiological measurement data collected by any of the sensors 115a- d (collectively, “the sensors 1 15”) can be used to at least partially control the sacral nerve stimulation therapy provided by the signal generator 110, as described in greater detail below with reference to Figures 3-5. In some embodiments, this may include closed-loop and / or open loop adjustment of stimulation parameters. Additionally or alternatively, this may include generating a predictive module that can be used to (a) predict when symptomatic episodes may occur in a patient, and (b) identify stimulation parameters that are expected to be effective in treating and / or preventing the symptomatic episode.

[0031] As one skilled in the art will appreciate from the disclosure herein, the system 100 can include any combination of the sensors 1 15. For example, in some embodiments, the system 100 can include multiple of the sensors 115 (e.g., the system 100 can include both the first sensor 1 15a and the third sensor 1 15c, or both the third sensor 115c and the fourth sensor 1 15d, or each of the first, second, and third, sensors 115a-c, or the like.) In other embodiments, the system 100 includes only a single sensor 115.

[0032] In some embodiments, the system 100 can be implanted in the patient P to treat IBD or an associated condition, including Crohn’s disease or ulcerative colitis. For example, the system 100 can deliver electrical signals to one or more sacral nerves of the patient to electrically stimulate the one or more sacral nerves. As described in detail throughout this Detailed Description, the electrical signal can treat, reduce, and / or ameliorate the IBD. For example, the electrical signal may reduce one or more IBD- related symptoms (e.g., diarrhea, abdominal pain, weight loss, etc.), and / or reduce inflammation causing the one or more symptoms. Moreover, although shown as providing unilateral stimulation, in some embodiments the system 100 can be configured to provide bilateral sacral nerve stimulation to treat the patient’s IBD.Additional details of electrical signals and stimulation regimes for treating IBD are described below with reference to Figures 2A and 2B.

[0033] In some embodiments, prior to receiving the signal generator 110, the patient P undergoes a trial period during which the patient P receives electrical stimulation to determine whether the patient P responds favorably to stimulation therapy. During the trial period, the patient P may use a temporary, external trial stimulator that generates and transmits electrical signals to the target neural population via the signal delivery device 120 or another implanted signal delivery element. If the patient responds favorably during the trial period, the patient may elect to have the signal generator 1 10 implanted to facilitate chronic stimulation therapy. In some embodiments, the trial period can be omitted, and the signal generator 1 10 can be implanted without the patient previously receiving stimulation from a temporary external signal generator.

[0034] Figure 1 C is an illustration of a sacral plexus SP of a patient, along with a distal portion of the lead 122 shown as implanted at a representative location. The sacral plexus SP includes four sacral spinal nerves: the first sacral nerve S1 , the second sacral nerve S2, the third sacral nerve S3, and the fourth sacral nerve S4. The lead 122 is shown as extending along (e.g., proximate to) the third sacral nerve S3 such that it can electrically stimulate the third sacral nerve S3. In other embodiments, however, the lead 122 can be positioned proximate other sacral spinal nerves, and / or proximate other nerve fibers of the sacral plexus SP, to electrically stimulate other target tissue. In yet other embodiments, the lead 122 can be positioned proximate other neural structures of the sacral plexus SP.

[0035] Figure 1 C also shows a plurality of electrodes or electrical contacts 124a-d carried by the lead 122, as described previously. Electrical signals generated by the signal generator 1 10 and transmitted through the lead 122 can be delivered to the target neural population via the electrodes 124a-d. Although shown as having four electrodes, the lead 122 can have more or fewer electrodes, such as one, two, three, four, five, six, seven, eight, or more.

[0036] In some embodiments, test stimulation may be administered to a patient during a procedure to implant the signal delivery device 120. This can be done to ensure adequate placement of the lead 122, e.g., to ensure that the electrical signals deliveredvia the lead 122 are applied to the target neural population. In some embodiments, test stimulation is administered at or above a sensory threshold during an implant procedure such that the patient can give intraoperative feedback about the location of the sensation, and thus the location of the lead 122. In some embodiments, test stimulation is administered at or above a motor threshold during the implant procedure, and a motor response to the test stimulation is observed to determine the location of the lead 122. In other embodiments, however, placement of the lead 122 can be confirmed using other techniques (e.g., imaging), such that intraoperative test stimulation is not required.

[0037] Figure 2A is a partially schematic illustration of a representative electrical signal waveform 200 (“the signal 200”) generated in accordance with embodiments of the present technology. The signal 200 can be generated by the system 100 (e.g., by the signal generator 110) described above with respect to Figures 1A and 1 B, or by another sacral neuromodulation system. As described throughout this Detailed Description, the signal 200 can be delivered to a patient’s sacral region to treat a patient condition such as IBD.

[0038] The signal 200 includes repeating pulse periods 201 , with each pulse period 201 having a biphasic pulse 202 followed by an interpulse interval 212. Each pulse 202 includes a first pulse phase 203 having a first polarity followed by a second pulse phase 204 having a second polarity that is opposite the first polarity. For example, in the illustrated embodiment the first pulse phase 203 is an anodic pulse phase and the second pulse phase 204 is a cathodic pulse phase, although in other embodiments the anodic pulse phase and the cathodic pulse phase can be reversed, such that the cathodic pulse phase is the first pulse phase and the anodic pulse phase is the second pulse phase. In other embodiments, the signal 200 includes monophasic pulses. In such embodiments, the signal 200 includes repeating pulses of the same polarity.

[0039] In some embodiments, the first pulse phase 203 is separated from the second pulse phase 204 by an interphase interval 208. During the interphase interval 208, the amplitude of the signal 200 can return to baseline (e.g., zero or about zero), although in other embodiments the amplitude of the signal 200 during the interphase interval 214 can be a non-zero value. In some embodiments, the interphase interval 208 is omitted, and the signal 200 transitions directly from the first pulse phase 203 to the second pulse phase 204.

[0040] The first pulse phase 203 can have a pulse width 206 within a pulse width range of from about 100 microseconds to about 2 milliseconds. For example, the first pulse phase 203 can have a pulse width 206 within a pulse width range of from about 100 microseconds to about 1 .5 milliseconds, or from about 100 microseconds to about 1 millisecond, or from about 100 microseconds to about 800 microseconds, or from about 200 microseconds to about 700 microseconds, or from about 200 microseconds to about 600 microseconds, or from about 300 microseconds to about 700 microseconds, or from about 300 microseconds to about 600 microseconds, or from about 300 microseconds to about 500 microseconds, or from about 400 microseconds to about 600 microseconds, or from about 400 microseconds to about 500 microseconds. For example, in some embodiments the pulse width 206 can be about 100 microseconds, about 150 microseconds, about 200 microseconds, about 250 microseconds, about 300 microseconds, about 350 microseconds, about 400 microseconds, about 450 microseconds, about 500 microseconds, about 550 microseconds, about 600 microseconds, about 650 microseconds, or about 700 microseconds. The foregoing pulse width ranges and values are provided by way of example only — in some embodiments, the electrical signals described herein may have pulse width values outside the foregoing ranges.

[0041] In some embodiments, the second pulse phase 204 has the same or about the same pulse width as the first pulse phase 203. Accordingly, the second pulse phase 204 can have any of the pulse widths recited above with respect to the first pulse phase 203. In other embodiments, however, the second pulse phase 204 can have a different pulse width than the first pulse phase 203. For example, if the first pulse phase 203 has a pulse width of 400 microseconds or less, the second pulse phase 204 may have a pulse width of 600 microseconds or more. Likewise, if the first pulse phase 203 has a pulse width of 600 microseconds or more, the second pulse phase 204 may have a pulse width of 400 microseconds or less. In general, when the second pulse phase 204 has a different pulse width than the first pulse phase 203, the pulse width of the second pulse phase 204 can be 50%, 60%, 70%, 80%, 90%, 1 10%, 120%, 130%, 140%, 150%, 160%, 170%, 180%, 190% or 200% of the pulse width of the first pulse phase 203.

[0042] Regardless of whether the first pulse phase 203 and the second pulse phase 204 have the same pulse width, a total charge delivered during the second pulse phase 204 can be equal or approximately equal in magnitude and opposite in polarityfrom the total charge delivered during the first pulse phase 203. In this way, the second pulse phase 204 is a charge balancing pulse that prevents or at least reduces charge buildup at the electrode used to deliver the signal 200. Accordingly, in embodiments for which the first pulse phase 203 and the second pulse phase 204 have an equal or approximately equal pulse width, the first pulse phase 203 and the second pulse phase 204 can have an equal or approximately equal and opposite amplitude. In embodiments in which the first pulse phase 203 and the second pulse phase 204 have different pulse widths, the first pulse phase 203 and the second pulse phase 204 can have different amplitudes such that the total charge delivered during the first pulse phase 203 and the second pulse phase 204 remains approximately the same. In other embodiments, the pulse 202 can be charge imbalanced, such that the first pulse phase 203 and the second pulse phase 204 do not deliver charges of the same magnitude. In such embodiments, charge buildup at the electrode may passively dissipate.

[0043] The interpulse interval 212 is a quiescent period between sequential pulses 202. During the interpulse interval 212, the signal 200 can return to a baseline amplitude (e.g., zero or about zero) such that little to no charge is administered to the patient. In some embodiments, the interpulse interval can be within an interpulse interval range of from about 1 millisecond to about 1 second, such as from about 5 milliseconds to about 500 milliseconds, or from about 50 milliseconds to about 500 milliseconds, or from about 100 milliseconds to about 300 milliseconds. The foregoing interpulse interval ranges and values are provided by way of example only — in some embodiments, the electrical signals described herein may have interpulse interval values outside the foregoing ranges. In some embodiments, the duration of the interpulse interval 212 can be set independently from the duration of the pulses 202. In other embodiments, the duration of the interpulse interval 212 is set based on a selected pulse 202 duration and desired signal frequency.

[0044] The duration of the pulse period 201 determines the frequency of the signal 200. For example, if the duration of the pulse period 201 is 200 milliseconds, then the frequency of the signal is 5 Hz (i.e., five pulse periods 201 are delivered per second). The signal 200 can have a frequency between about 0.5 Hz and about 50 Hz. For example, the signal 200 can have a frequency within a frequency range of from about 1 Hz to about 40 Hz, or from about 1 Hz to about 30 Hz, or from about 1 Hz to about 25 Hz, or from about 1 Hz to about 20 Hz, or from about 1 Hz to about 15 Hz, or from about5 Hz to about 15 Hz, or from about 1 Hz to about 12 Hz, or from about 1 Hz to about 10 Hz, or from about 2 Hz to about 8 Hz, or from about 3 Hz to about 7 Hz, or from about 4 Hz to about 6 Hz, or from about 4.5 Hz to about 5.5 Hz, or from about 4.8 Hz to about 5.2 Hz. In other embodiments, the signal 200 can have a frequency of about 0.5 Hz, about 1 Hz, about 2 Hz, about 3 Hz, about 4 Hz, about 5 Hz, about 6 Hz, about 7 Hz, or about 8 Hz. In some embodiments, the signal 200 can have a frequency of about 4.2 Hz, about 4.4 Hz, about 4.6 Hz, about 4.8 Hz, about 5.0 Hz, about 5.2 Hz, about 5.4 Hz, about 5.6 Hz, or about 5.8 Hz. The foregoing frequency ranges and values are provided by way of example only — in some embodiments, the electrical signals described herein may have frequency values outside the foregoing ranges.

[0045] The pulses 202 can have a current amplitude between about 0.1 mA and about 20 mA. For example, in some embodiments the pulses 202 have a current amplitude within a current amplitude range of from about 0.5 mA to about 15 mA, or from about 1 mA to about 12 mA, or from about 2 mA to about 12 mA, or from about 3 mA to about 10 mA. The pulses 202 can also have a voltage amplitude between about 0.1 V and 15 V. For example, in some embodiments the pulses 202 have a voltage amplitude within a voltage amplitude range of from about 0.1 V to about 10 V, or from about 0.2 V to about 8 V, or from about 0.5 V to about 4 V. In some embodiments, the amplitude (e.g., the current amplitude and / or the voltage amplitude) of the signal 200 is set based on an individual patient’s sensory threshold and / or motor threshold. For example, in some embodiments the pulses 202 have a peak amplitude that is below the sensory or perception threshold of the patient. In such embodiments, the patient generally cannot actively feel the signal 200 as it is being administered. For example, the pulses 202 may have an amplitude that is 50% of sensory threshold, 60% of sensory threshold, 70% of sensory threshold, 80% of sensory threshold, 90% of sensory threshold, or 95% of sensory threshold. In other embodiments, the pulses 202 have an amplitude that is at or above the sensory threshold, such that the patient can perceive the signal 200 being delivered. In yet other embodiments, the pulses 202 have an amplitude that is below the motor threshold of the patient. In such embodiments, the signal 200 does not induce clinically discernable movement (e.g., muscle twitching) in the patient while being administered. For example, the pulses 202 may have an amplitude that is 50% of motor threshold, 60% of motor threshold, 70% of motor threshold, 80% of motor threshold, 90% of motor threshold, or 95% of motor threshold.

[0046] In some embodiments, electrical signals generated in accordance with the present technology can have one more ramped parameters. For example, Figure 2B illustrates an electrical signal 250 (“the signal 250”) with a ramped amplitude in accordance with some embodiments of the present technology. The signal 250 can be generally similar to the signal 200, and can have any of the parameters and parameter values described above in connection with the signal 200. However, relative to the signal 200, an amplitude of the of the signal 250 can be ramped such that a peak amplitude of the signal 250 changes over time. In the illustrated embodiment, for example, the signal 250 includes a plurality of pulses 252 (five pulses 252a-252e are shown), with each sequential pulse 252 having a different amplitude than the preceding pulse 252. More specifically, the amplitude of the signal 250 increases from pulse 252a to pulse 252c, and then decreases from pulse 252c to pulse 252e. This pattern can then be repeated. In some embodiments, the signal 250 includes multiple pulses 252 at a common amplitude before being ramped up or down to a different amplitude (e.g., multiple pulses are delivered with an amplitude equal to the pulse 252a before the signal 250 is ramped to delivering pulses with an amplitude equal to the pulse 252b). Although shown as being ramped in two directions, in other embodiments the signal 250 is ramped only in a single direction (e.g., the amplitude is either increased or decreased, but not both), until a maximum or minimum amplitude is reached.

[0047] In some embodiments, other parameters of the signal 250 (e.g., pulse width, interpulse interval, frequency, etc.) can remain constant (e.g., unchanged) as the amplitude of the pulses 252 is ramped. In other embodiments, one or more other parameters can be ramped, in addition to the amplitude being ramped. For example, in some embodiments both a pulse width and an amplitude of the pulses 252 is ramped. In such embodiments, the pulse width of the pulses 252 may be inversely ramped with the amplitude, such that as the amplitude increases, the pulse width decreases, and vice versa. Moreover, in some embodiments the pulse width, frequency, or other parameter is ramped instead of the amplitude.

[0048] In some embodiments, the electrical signals described herein (e.g., the signal 200 of Figure 2A and the signal 250 of Figure 2B) are administered during discrete stimulation sessions or periods that have a duration less than 24 hours. For example, the stimulation sessions may have a duration of between about 15 minutes and about 4 hours, or between about 15 minutes and about 3 hours, or between about15 minutes and about 2 hours, or between about 30 minutes and about 3 hours, or between about 30 minutes and about 2 hours, or between about 30 minutes and about 1.5 hours, or between about 45 minutes and about 1 .5 hours. In some embodiments, the stimulation sessions can have a duration of about 5 minutes, about 15 minutes, about 30 minutes, about 45 minutes, about 1 hour, about 1.5 hours, about 2 hours, about 2.5 hours, about 3 hours, about 3.5 hours, or about 4 hours. The patient can receive one or more stimulation sessions per day. For example, in some embodiments the patient receives a single stimulation session per day. In other embodiments, the patient receives multiple (e.g., two, three, four, etc.) discrete stimulation sessions per day. During periods between stimulation sessions, the patient generally does not receive any stimulation, or at least any clinically meaningful stimulation. The foregoing representative stimulation period durations are provided by way of example only — in some embodiments, the electrical signals described herein may be applied during stimulation sessions having different durations. One expected advantage of delivering stimulation during discrete stimulation sessions having a relatively short duration is that doing so may reduce the frequency with which the patient must recharge the power source in the signal generator. Another expected advantage is that it may reduce the likelihood the patient becomes desensitized (e.g., habituates) to the stimulation. In some embodiments, however, electrical stimulation is applied for 24 hours per day.

[0049] The electrical signals can be administered intermittently or continuously during the stimulation sessions. For example, the electrical signals can be administered continuously (e.g., without interruption) during the entirety of the stimulation session. Alternatively, the electrical signals can be administered intermittently, such that the signal is only actively delivered during portions of the stimulation sessions. In such embodiments, the stimulation session may cycle between “on” times during which the signal is being administered, and “off” times during which the signal is not being administered. In some embodiments, the “on” time can be between about 1 second and about 10 minutes, and the “off” time can be between about 1 second and about 10 minutes. Representative examples of suitable intermittent stimulation schedules include 10 seconds on, 10 seconds off; 10 seconds on, 30 seconds off; 10 seconds on, 60 seconds off; 10 seconds on, 90 seconds off; 30 seconds on, 30 seconds off; 30 seconds on, 60 seconds off; 30 seconds on, 90 seconds off; 1 minute on, 1 minute off; 10 minutes on, 10 minutes off, etc. The on times and off times are provided by way of exampleonly — in some embodiments, the electrical signals described herein may be applied according to different on times and off times.

[0050] Regardless of whether the signal is administered intermittently or continuously during the stimulation sessions, the signal can be administered according to a duty cycle of between about 0.1 % and about 100% during each stimulation session. As used herein, and referring again to Figure 2A, the term duty cycle refers to the fraction of a single pulse period 201 (which consists of a single pulse 202 and a single interpulse interval 212) in which the pulse 202 is being actively delivered. That is, for a single pulse period, the duty cycle can be expressed as: (pulse width / duration of pulse period) x 100. For example, if a pulse period comprises (1 ) a bi-phasic pulse with no interphase interval and with each phase of the pulse having a pulse width of 500 microseconds, followed by (2) an interpulse interval having a duration of 99 milliseconds (e.g., before the following pulse period begins), the duty cycle is 1 % (1 millisecond combined pulse width / 100 millisecond pulse period duration, x 100). In this way, the term duty cycle is different than the term intermittent, which generally refers to delivering sequential pulse periods in a row for a first duration (e.g., 10 seconds), followed by a quiescent period during which no pulse periods are delivered for a second duration (e.g., for 90 seconds).C. Controlling Sacral Nerve Stimulation Parameters Based on Measured Physiologic Parameters

[0051] In some embodiments, the sacral nerve stimulation described herein can be controlled based on measured physiologic parameters. As used herein, “controlling” sacral nerve stimulation can include initiating delivery of sacral nerve stimulation, ceasing delivery of sacral nerve stimulation, and / or adjusting one or more signal delivery parameters. Example signal delivery parameters that can be adjusted include, but are not limited to, amplitude, pulse width, frequency, duty cycle, and electrode combinations. In some embodiments, the adjustments can include a change in the time that stimulation is initiated or terminated relative to a particular time of day or another reference event, such as when the patient consumes a meal. Representative physiological parameters that can be used to at least partially control stimulation include, but are not limited to, heart rate, heart rate variability, body temperature, body position, body movement, electrical signals (e.g., neural activity from muscles ornerves), peristaltic activity of the gut, gut evacuation, gut motility, sounds from internal organs, visual appearance of internal or external organs, electrical impedance between tissues, respiratory rate, blood oxygen level, biomarker concentrations. These physiological parameters can be measured using various sensors operably coupled to a computing device associated with the sacral nerve stimulation system, such as any of the sensors 115 described above with reference to Figures 1 A and 1 B. Without intending to be bound by theory, controlling sacral nerve stimulation based on one or more measured parameters is excepted to tailor to the sacral nerve stimulation to the needs of a particular patient to improve the effectiveness of the treatment.

[0052] Figure 3 is a flowchart of an example method 300 of controlling sacral nerve stimulation in a patient based at least in part on one or more measured physiological parameters and in accordance with embodiments of the present technology. The method 300 can begin at block 302 by determining the physiological parameters to be measured. The physiological parameters can include any of those identified throughout this Detailed Description. For example, the physiologic parameters can include (i) the presence or absence of blood in the Gl tract, (ii) the temperature of the Gl tract, (iii) peristaltic wave frequency, strength, and / or timing, (iv) pH of gut contents throughout the Gl tract, (v) gas molecules in the gut, (vi) enzymes and / or cytokines in the gut, (vii) electrical activity of the gut, (viii) sounds within the gut, (ix) gut motility, (x) images of portions of the Gl tract, (xi) videos of portions of the Gl tract. Additional physiologic parameters can include heart rate, heart rate variability, body temperature, body position, body movement, electrical signals (e.g., neural activity from muscles or nerves), peristaltic activity of the gut, gut evacuation (e.g., bowel movements), sounds from internal organs, visual appearance of internal or external organs, electrical impedance between tissues, respiratory rate, blood oxygen level, various biomarker concentrations (e.g., cytokines, chemokines, or other molecules), or the like.

[0053] In some embodiments, the operation at block 302 is performed by a computing system associated with a sacral nerve stimulator (e.g., the external controller 104 of Figures 1 A and 1 B). The computing system can provide one or more recommended physiological parameters to be measured, e.g., based on which type of data may be useful in controlling stimulation for a particular patient, and / or based on which types of sensors are available. In other embodiments, a healthcare provider (e.g.,a physician) may select which physiological parameters are to be measured, and input the selected parameters into a controller for the sacral nerve stimulator.

[0054] The method 300 continues at block 304 by determining a data collection mechanism for measuring the physiologic parameters selected at block 302. This can include, for example, selecting which device and sensor to use to collect the data. For example, for the system 100 described above with reference to Figures 1 A-1 C, the operation at block 304 may include selecting one or more of the sensors 115 (and the associated device that carries the particular sensor 1 15) to measure the selected physiologic parameter. Thus, in various embodiments the data collection mechanism can include any of the sensors 115 described above with reference to Figures 1 A and 1 B, including but not limited to sensors located on an implanted device (e.g., the sensors 1 15a and / or 115b), sensors located on an external wearable device (e.g., the sensor 115c), and / or sensors located on a swallowable capsule (e.g., the sensor 1 15d). The data collection mechanism can include any number of sensors, such as one, two, three, four, or more sensors, and any combination of implanted, wearable, and / or swallowable sensors (e.g., one sensor 1 15a, two sensors 115b, one sensor 1 15c, and one sensor 1 15d implemented as a swallowable pill or capsule 102).

[0055] In some embodiments, the data collection mechanism is selected based on the physiologic parameters to be measured (e.g., the determined physiologic parameters in block 302). For example, the operation at block 304 may include selecting a data collection mechanism that is suitable to measure the physiological parameter. As a non-limiting example, if the physiological parameter determined at block 302 is gut pH, then the data collection mechanism may include a swallowable capsule with a pH sensor. As another non-limiting example, if the physiological parameter is gut motility based on gut sounds, then the data collection mechanism may include a microphone carried by a wearable device. In some embodiments, the data collection mechanism is selected from a subset of available data collection mechanisms, which can include some or all of the sensors 115 described above with reference to Figures 1 A and 1 B.

[0056] The method can continue at block 306 by measuring the determined physiologic parameters (e.g., from block 302) using the determined data collection mechanism (e.g., from block 304). For example, an implanted device (e.g., sensor 1 15a and / or sensor 115b) measures heart rate, heart rate variability, and body temperature.As another example, a swallowable pill (e.g., capsule 102) measures the pH of gut contents, the electrical activity of the gut, and sounds within the gut.

[0057] In some embodiments, the timing of the operation at block 306 can be at least partially controlled by the data collection mechanism. For example, if the data collection mechanism includes a sensor on a swallowable capsule, the swallowable capsule may only initiate measuring and recording physiologic parameter data after a pre-determined amount of time has elapsed (e.g., time elapsed since the patient swallowed the capsule). As another example, the swallowable capsule can have a dissolvable coating that is configured to dissolve after exposure to certain bodily fluids (e.g., stomach acid) to expose one or more sensors carried by the capsule, which can begin measuring the physiologic parameters once exposed. In an additional example, the location of the capsule can be monitored via external sensors and used to determine when to begin data collection. Without intending to be bound by theory, these methods of controlling the timing of data collection may allow for targeted parameter measurement of select portions of the Gl tract, or other anatomical portions of a patient.

[0058] The method 300 can continue at block 308 by controlling the sacral nerve stimulation therapy based at least in part on the measured physiologic parameters. As set forth above, this may include initiating a stimulation session, ceasing a stimulation session, and / or adjusting one or more signal delivery parameters. Example signal delivery parameters that can be adjusted include, but are not limited to, amplitude, pulse width, frequency, duty cycle, and electrode combinations.

[0059] As a particular non-limiting example, elevated peristaltic frequency may indicate Gl distress, high bowel movement frequency, and / or bowel urgency. Accordingly, if the data collection mechanism measures elevated peristaltic frequency, the operation at block 308 may include initiating a stimulation session (e.g., if stimulation is not actively being administered to the patient) and / or increasing a dosage of the stimulation (e.g., increasing the amplitude). As another non-limiting example, increased bowel sounds may be correlated with increased and / or uncontrolled bowel evacuation and / or gut motility. In such embodiments, the operation at block 308 may include initiating a stimulation session and / or increasing a dosage of the stimulation in response to detecting an increase in bowel sounds. In yet another non-limiting example, abnormal pH of a specific portion of the Gl tract may be correlated with Gl distress and / or bowelurgency. Accordingly, the operation of block 308 may include initiating a stimulation session and / or increasing a dosage of the stimulation in response to the pH measurement. In an additional non-limiting example, electrical signals corresponding to a patient’s resting heart rate and normal heart rate variability may be paired with peristaltic activity measurements to indicate cessation of Gl distress and / or bowel urgency. In such embodiments, the operation of block 308 may include ceasing a stimulation session and / or decreasing a dosage of the stimulation. As the foregoing examples demonstrate, controlling the sacral nerve stimulation therapy based at least in part on the measured physiologic parameters may provide real-time or at least substantially real-time relief to the patient.

[0060] In some embodiments, the operation at block 308 can be automatic such that the operations at blocks 306 and 308 form a “closed-loop” stimulation control mechanism. For example, the physiological measurement data collected by the sensors can be transmitted to a control system (e.g., the external controller 104 of Figure 1 A and 1 B), which can analyze the physiological measurement data to determine a recommended therapy change. The control system can then control the signal generator to automatically implement the therapy change, e.g., by initiating a stimulation session, terminating a stimulation session, and / or changing one or more parameters of stimulation.

[0061] In some embodiments, the operation at block 308 is not fully automated such that the operations at blocks 306 and 308 form an “open-loop” stimulation control mechanism. For example, the physiological measurement data collected by the sensors can be transmitted to an external device (e.g., the external controller 104 of Figure 1 A and 1 B) for display to a healthcare provider. The healthcare provider can analyze the physiological measurement data to determine the recommended therapy change. In some embodiments, the system can provide a recommended therapy change to the healthcare provider or the patient, but the healthcare provider or patient must “approve” the therapy change (e.g., using a physician or patient controller) before the signal generator implements the therapy change.

[0062] The present technology can also be used to generate predictive models that can be used to control sacral nerve stimulation. For example, Figure 4 is a flowchart of an example method 400 of building and using a predictive model to control sacralnerve stimulation in accordance with embodiments of the present technology. As described in detail below, the physiologic parameter measurements / data can be collected over time and used to build a predictive model that can predict when an individual patient tends to experience symptoms and / or specific activities that trigger symptoms. Without intending to be bound by theory, the predictive information can be used to pre-emptively provide sacral nerve stimulation therapy, e.g., to alleviate patient distress before it occurs. In some embodiments, the predictive models can be implemented as one or more algorithms that utilize inputs (e.g., physiologic measurements) to determine outputs (e.g., controlling sacral nerve stimulation). In other embodiments, the predictive models can be implemented as an artificial intelligence (Al) and / or machine learning (ML) model. The Al models can be trained using previously collected data for a particular patient or a plurality of reference patients. The Al model can be locked (e.g., not continuously updating itself) or be federated such that over time it adapts to a particular patient’s responses.

[0063] The method 400 can include determining physiological parameters to be measured at block 402, determining a data collection mechanism for measuring the physiological parameters at block 404, and measuring the physiological parameters using the data collection mechanism at block 406. In some embodiments, the operations at blocks 402, 404, and 406 can be the same as, or generally similar to, the operations at blocks 302, 304, and 306 of Figure 3, described above. Accordingly, one skilled in the art will appreciate that the description of blocks 302, 304, and 306 with respect to Figure 3 apply equally to blocks 402, 404, and 406 of the Figure 4.

[0064] At block 408, the method 400 can include correlating the measured physiologic parameters (e.g., from block 406) with patient states and / or with one or more sacral nerve stimulation therapy parameters. For example, the operation at block 408 can include correlating the presence of certain physiologic parameters (e.g., increased peristaltic frequency, increased bowel sounds, etc.) with symptomatic patient episodes (e.g., Gl distress, urgency, incontinence, etc.). In some embodiments, symptomatic episodes are determined using objective criteria such as bowel movement frequency or blood in stool. In some embodiments, symptomatic episodes are identified using patient-reported information such as pain, energy level, stimulation comfort, sleep quality, fatigue, bowel urgency, bloating, constipation, etc. As described below, correlating measured physiological parameters with particular patient states can assistin building a predictive model that can predict the onset of symptomatic episodes based on measured physiologic parameters.

[0065] In addition to or in lieu of correlating the measured physiologic parameters with symptomatic episodes, in some embodiments the operation at block 408 includes correlating the measured physiologic parameters with particular stimulation parameters (e.g., amplitude, frequency, pulse width, electrode combinations, etc.). For example, if the measured physiological parameters and / or patient-reported feedback indicate a symptomatic episode (e.g., increased peristaltic frequency and / or bowel sounds indicating Gl distress) while receiving stimulation, the stimulation parameters and the episode can be recorded. Likewise, if the physiologic parameters and / or patient- reported feedback indicate the absence of a symptomatic episode while receiving stimulation, the stimulation parameters and absence of symptomatic episodes can be recorded. In some embodiments, patient-reported feedback of symptomatic episodes can be correlated with stimulation parameters or changes in stimulation parameters directly, e.g., without physiologic measurements / data provided by the one or more sensors 1 15a-c. In this way, a database that correlates different stimulation parameters with the presence or absence of symptoms can be built, as described below.

[0066] The method can continue at block 410 by building and / or updating a predictive model based on the correlations established between the measured physiologic parameters, the stimulation parameters, and / or the patient states. The predictive model can be a software module or algorithm that can be used to predict the onset of symptomatic episodes for a particular patient based on measured physiological parameters, and / or recommend particular therapy parameters that are expected to be effective for a particular patient. As set forth above, in some embodiments the predictive model can include one or more Al or ML models. The predictive module can be stored and / or executed locally or remotely. For example, the predictive model can be included within one or more connected devices of a sacral nerve stimulation system, such as the external control 104 of Figures 1 A and 1 B. The predictive model can also be stored and / or executed within a database (e.g., a server and / or the cloud).

[0067] In some embodiments, building or updating the predictive model includes cataloging the correlations between a particular physiological parameter value and symptomatic episodes. For example, if the operation at block 408 determines that anincrease in peristaltic frequency above a certain threshold indicates the impending onset of Gl distress, such correlation and threshold can be recorded in the predictive model. As another example, if the operation at block 408 determines that heart rate and body temperature are associated with bowel movement frequency, such correlation can be recorded in the predictive model. As a result, the predictive model can determine that a given patient is likely to experience a particular symptomatic episode if specific physiological measurements occur.

[0068] In some embodiments, building or updating the predictive model includes cataloging the correlations between a particular physiological parameter value and stimulation parameters. For example, if the operation at block 508 determines that a peristaltic frequency often increases if a stimulation amplitude falls below a particular amplitude threshold, such correlation and threshold can be recorded in the predictive model. As a result, the predictive model can also determine which stimulation parameters are effective in addressing particular patient symptoms.

[0069] In some embodiments, the predictive model is updated (discreetly and / or continuously) with new physiologic measurement data, patient state information, stimulation parameters, and / or correlations as data is accumulated over time. Without intending to be bound by theory, the more “input” correlations provided to the predictive model is expected to improve the accuracy and effectiveness of the predictive model. Accordingly, the operations at blocks 406, 408, and 410 can be iteratively repeated over time to improve the accuracy of the predictive model.

[0070] In some embodiments, the predictive models are specific for an individual patient to be treated. That is, the predictive model is built and updated using only correlations determined for the individual patient. In other embodiments, however, the predictive model can be built and updated using correlations established from a plurality of reference patients that may or may not include the individual patient to be treated. In such embodiments, the predictive models can still provide “patient-specific” recommendations for the individual patient by comparing the patient to similarly situated patients of the plurality of reference patients.

[0071] The method can continue at block 412 by using the predictive model to at least partially control sacral nerve stimulation therapy. For example, the predictive model can be used to start stimulation therapy, stop stimulation therapy, or change aparameter of stimulation therapy in anticipation of the onset of symptoms. Accordingly, in some embodiments the predictive model can be used to pre-emptively provide therapy, e.g., to alleviate patient symptoms before they occur. This can be used in combination with other programmed therapy or as a standalone therapy.

[0072] In addition to controlling sacral nerve stimulation, the present technology can also be used to determine which of a plurality of stimulation programs may be most effective for a given patient using measured physiological parameters. For example, as described in greater detail below, physiologic measurement data can be collected while each of the plurality of candidate sacral nerve stimulation programs is administered to the patient. The physiologic measurement data can be used in combination with other patient data to select a particular stimulation program.

[0073] Figure 5 is a flowchart of an example method of identifying an effective sacral nerve stimulation program from a plurality of candidate sacral nerve stimulation programs in accordance with some embodiments of the present technology. The method 500 can include determining physiological parameters to be measured at block 502 and determining a data collection mechanism for measuring the physiological parameters at block 504. In some embodiments, the operations at blocks 502 and 504 can be the same as, or generally similar to, the operations at blocks 302 and 304 of Figure 3, described above.

[0074] The method can continue at block 506 by determining and / or selecting a plurality of candidate sacral nerve stimulation programs to be tested. Each stimulation program can include a unique set of stimulation parameters (e.g., amplitude, frequency, pulse width, electrode combination, session length, etc.). For example, a first stimulation program may include a first set of stimulation parameters (e.g., a first stimulation amplitude, a first stimulation frequency, a first stimulation site), a second stimulation program may include a second set of stimulation parameters (e.g., a second stimulation amplitude, a second stimulation frequency, a second stimulation site), a third stimulation program may include a third set of stimulation parameters (e.g., the first stimulation amplitude, the second stimulation frequency, a third stimulation site), and so on. While not every individual stimulation parameter is necessarily different between different stimulation programs (e.g., the first stimulation frequency may be the same as the second stimulation frequency), at least one stimulation parameter is different so that notwo stimulation programs are identical. The number of stimulation programs selected at block 506 can include two, three, four, five, six, seven, eight, or more stimulation programs.

[0075] The method can continue at block 508 by delivering sacral nerve stimulation according to an individual one of the plurality of stimulation programs (e.g., the first stimulation program), and measuring the determined physiologic parameters (e.g., from block 502) using the data collection mechanism (e.g., from block 504) for a period of time. For example, the first stimulation program can be delivered for a first period of time while measuring the physiological parameters, the second stimulation program can be delivered for a second period of time while measuring the physiological parameters, and the third stimulation program can be delivered for a third period of time while measuring the physiological parameters. In some embodiments, the first, second, and third periods of time occur in series, e.g., such that the first, second, and third stimulation programs are delivered sequentially. In some embodiments, each of the first, second, and third periods of time are approximately the same duration. In additional embodiments, the duration of each of the periods of time are different relative to each other. In some embodiments, each of individual stimulation programs of the plurality of stimulation programs is programmed to occur at pre-defined intervals.

[0076] The method can continue at block 510 by receiving patient data reflecting a patient state during the period of time. In some embodiments, patient states are determined using objective criteria such as bowel movement frequency or blood in stool. In some embodiments, determining patient states includes using patient-reported information such as pain, energy level, stimulation comfort, sleep quality, fatigue, bowel urgency, bloating, constipation, etc. Patient data is generated based on one or more of the patient states for each of the individual stimulation programs of the plurality of stimulation programs for each of the periods of time.

[0077] As demonstrated by block 512, the process of (1 ) delivering stimulation therapy according to an individual stimulation program of the plurality of stimulation programs and measuring the determined physiologic parameters for a period of time, and (2) receiving patient data that reflects a patient state for the period of time is repeated until each of the stimulation programs of the plurality of stimulation programs has been delivered. In this way, each of the stimulation programs is “screened” or“tested,” while collecting a common set of objective (physiological measurements) and subjective (patient-reported) data. In some embodiments, the plurality of stimulation programs can be provided “blinded” to the patient, in that the patient is unaware of one or more aspects of a given stimulation program delivered to the patient (e.g., the set of stimulation parameters included in a given stimulation program, the length of the one or more periods of time, etc.), e.g., to avoid any bias in the collected subjective data.

[0078] At block 514, once each of the stimulation programs of the plurality of stimulation programs has been tested, one of the stimulation programs is selected for the patient based at least in part on the corresponding measured physiologic parameters and received patient data. For example, the stimulation programs can be evaluated based on the corresponding physiological measurements and patient- reported data, and the most effective and / or tolerable stimulation program of the plurality of stimulation programs can be selected, e.g., for chronic or ongoing therapy.D. Representative Examples

[0079] The following examples are provided to further illustrate embodiments of the present technology and are not to be interpreted as limiting the scope of the present technology. To the extent that certain embodiments or features thereof are mentioned, it is merely for purposes of illustration and, unless otherwise specified, is not intended to limit the present technology. It will be understood that many variations can be made in the procedures described herein while still remaining within the bounds of the present technology. Such variations are intended to be included within the scope of the presently disclosed technology.1 . A method of treating inflammatory bowel disease (IBD) in a patient using sacral nerve stimulation (SNS) treatment, the method comprising: providing a swallowable capsule to the patient, the swallowable capsule carrying at least one sensor for measuring one or more physiologic parameters associated with a Gl tract of the patient, after the patient has swallowed the swallowable capsule, measuring the one or more physiologic parameters using the sensor; and controlling the SNS treatment based at least in part on the measured physiologic parameters, wherein controlling the SNS treatment includes at least oneof initiating a stimulation session, ceasing a stimulation session, or adjusting one or more stimulation parameters of the SNS treatment.2. The method of example 1 wherein controlling the SNS treatment includes adjusting one or more stimulation parameters, and wherein the one or more stimulation parameters include at least one of amplitude, frequency, pulse width, duty cycle, and / or electrode combination.3. The method of example 1 wherein controlling the SNS treatment includes initiating a stimulation session based at least in part on the measured physiologic parameter.4. The method of any of examples 1 -3 wherein the one or more physiologic parameters include one or more of: (i) a presence or absence of blood in the Gl tract, (ii) a temperature of the Gl tract, (iii) a peristaltic wave frequency, strength, and / or timing, (iv) a pH of gut contents throughout the Gl tract, (v) gas molecules in the gut, (vi) enzymes and / or cytokines in the gut, (vii) electrical activity of the gut, (viii) sounds within the gut, (ix) gut motility, (x) images of portions of the Gl tract, (xi) videos of portions of the Gl tract.5. The method of any of examples 1 -4 wherein measuring the one or more physiologic parameters using the swallowable capsule further includes measuring a select portion of the Gl tract.6. The method of example 5 wherein the swallowable capsule is programmed to begin measuring the one or more physiological measurements after a predetermined time has elapsed since the patient swallowed the capsule.7. The method of example 5 wherein the swallowable capsule includes a dissolvable coating configured to dissolve after exposure to certain bodily fluids to expose the at least one sensor.8. The method of any of examples 1 -7, further comprising: correlating the one or more measured physiologic parameters with one or more stimulation parameters and with one or more patient states; and generating a predictive model based on the correlation between the measured physiologic parameters and the one or more stimulation parameters, and based on the correlation between the measured physiologic parameters and the one or more patient states; wherein controlling the SNS treatment further includes controlling the SNS treatment at least in part on an output of the predictive model.9. The method of example 8, further comprising: continuously or periodically updating the predictive model based on additional physiologic parameter measurements and additional patient states.10. A method of treating inflammatory bowel disease (IBD) in a patient using sacral nerve stimulation (SNS) treatment, the method comprising: providing a swallowable capsule having at least one sensor configured to measure one or more physiologic parameters associated with a Gl tract of the patient; and programming a sacral nerve stimulation system to control delivery of electrical stimulation to a sacral nerve of the patient based at least in part on the one or more physiologic parameters measured by the swallowable capsule.11. The method of example 10 wherein programming the sacral nerve stimulation system includes programming the system to automatically initiate a stimulation session in response to the one more physiologic parameters meeting a predetermined threshold.12. The method of example 10 wherein programming the sacral nerve stimulation system includes programming the system to automatically terminate a stimulation session in response to the one or more physiologic parameters meeting a predetermined threshold.13. The method of example 10 wherein programming the sacral nerve stimulation system includes programming the system to automatically adjust a stimulation parameter of the electrical stimulation based on the one or more physiologic parameters.14. The method of any of examples 10-13 wherein the one or more physiologic parameters include one or more of: (i) a presence or absence of blood in the Gl tract, (ii) a temperature of the Gl tract, (iii) a peristaltic wave frequency, strength, and / or timing, (iv) a pH of gut contents throughout the Gl tract, (v) gas molecules in the gut, (vi) enzymes and / or cytokines in the gut, (vii) electrical activity of the gut, (viii) sounds within the gut, (ix) gut motility, (x) images of portions of the Gl tract, (xi) videos of portions of the Gl tract.15. The method of any of examples 10-14 wherein the swallowable pill is configured to measure the one or more physiologic parameters at one or more select portions of a Gl tract of the patient.16. The method of example 15 wherein the swallowable pill is configured to measure the one or more physiologic parameters at one or more predetermined time intervals.17. The method of example 15 wherein the swallowable pill includes a dissolvable coating configured to dissolve upon exposure to bodily fluids within the Gl tract to expose the at least one sensor.18. A system for treating inflammatory bowel disease (IBD) in a patient, the system comprising: an implantable signal delivery element positionable proximate a sacral nerve of the patient; a signal generator programmed with first instructions that, when executed, cause the signal generator to generate and deliver an electrical signal to the sacral nerve of the patient via the implantable signal delivery element; and-SO-a controller for controlling the signal generator, wherein the controller is programmed with second instructions that, when executed, cause the controller to — receive one or more measured physiologic parameters collected from a swallowable pill ingestible by the patient and having at least one sensor; and based on the one or more measured physiologic parameters collected from the swallowable pill, control the signal generator to initiate a stimulation session, cease a stimulation session, or adjust one or more stimulation parameters of the electrical signal.19. The system of example 18, further comprising the swallowable pill.20. The system of example 19 wherein the swallowable pill is configured to measure the one or more physiologic parameters at one or more predetermined locations along a Gl tract of the patient.21 . The system of example 19 or example 20 wherein the swallowable pill is programmed to automatically measure the one or more physiologic parameters at one or more predetermined time intervals.22. The system of example 19 or example 20 wherein the swallowable pill includes a dissolvable coating configured to dissolve upon exposure to bodily fluids within the Gl tract of the patient to expose the at least one sensor.23. The system of any of examples 18-22 wherein the one or more physiologic parameters include one or more of: (I) a presence or absence of blood in the Gl tract, (ii) a temperature of the Gl tract, (iii) a peristaltic wave frequency, strength, and / or timing, (iv) a pH of gut contents throughout the Gl tract, (v) gas molecules in the gut, (vi) enzymes and / or cytokines in the gut, (vii) electrical activity of the gut, (viii) sounds within the gut, (ix) gut motility, (x) images of portions of the Gl tract, (xi) videos of portions of the Gl tract.24. The system of any of examples 18-23 wherein the second instructions cause the controller to direct the signal generator to initiate a stimulation session in response to the one or more measured physiologic parameters meeting a predetermined threshold.25. The system of any of examples 18-23 wherein the second instructions cause the controller to direct the signal generator to terminate a stimulation session in response to the one or more measured physiologic parameters meeting a predetermined threshold.26. The system of any of examples 18-23 wherein the second instructions cause the controller to direct the signal generator to adjust a stimulation parameter of the electrical signal based on the one or more measured physiologic parameters.27. The system of any of examples 18-26 wherein the operation of receiving the one or more measured physiologic parameters collected from the swallowable pill includes receiving the one or more measured physiologic parameters directly from the swallowable pill.28. The system of any of examples 18-26 wherein the operation of receiving the one or more measured physiologic parameters collected from the swallowable pill includes receiving the one or more measured physiologic parameters from a computing system distinct from the swallowable pill.29. A system for treating inflammatory bowel disease (IBD), the system comprising: a processor; and a non-transitory computer-readable medium storing a predictive model and instructions that, when executed by the processor, cause the system to: receive first treatment data from at least one patient receiving sacral nerve stimulation for treating IBD, wherein the first treatment data includes one or more first measured physiologic parameters and at least one of a patient state or a patient stimulation parameter,establish a correlation between the one or more first measured physiologic parameters and the patient state and / or the patient stimulation parameter, and update the predictive model based on the correlation between the one or more first measured physiologic parameters and the patient state and / or the patient stimulation parameter, wherein the predictive model is configured to predict an onset of a symptomatic episode associated with the patient’s IBD and / or recommend a particular therapy parameter for treating the patient’s IBD, based on second treatment data that includes one or more second measured physiologic parameters collected at a different point in time than the first treatment data.30. The system of example 29 wherein the first treatment data includes the patient state.31 . The system of example 30 wherein the patient state includes an indication of a symptomatic episode.32. The system of example 29 wherein the first treatment data includes the patient stimulation parameter.33. The system of example 32 wherein the patient stimulation parameter includes an amplitude, frequency, pulse width, and / or electrode combination of the sacral nerve stimulation.34. The system of any of examples 29-33 wherein the first treatment data includes both the patient state and the patient stimulation parameter, and wherein the operation of establishing a correlation includes establishing a correlation between each of the one or more first measured physiologic parameters, the patient state, and the patient stimulation parameter.35. The system of any of examples 29-34 wherein the predictive model is configured to predict the onset of a symptomatic episode associated with the patient’s IBD based on the second treatment data.36. The system of any of examples 29-34 wherein the predictive model is configured to recommend the particular therapy parameter for treating the patient’s IBD based on the second treatment data.37. The system of any of examples 29-34 wherein the predictive model is configured to both predict the onset of a symptomatic episode for the patient and to recommend the particular therapy parameter for the patient based on the second treatment data.38. The system of any of examples 29-37 wherein the predictive model includes an artificial intelligence and / or machine learning model.E. Conclusion

[0080] From the foregoing, it will be appreciated that specific embodiments of the disclosed technology have been described herein for purposes of illustration, but that various modifications may be made without deviating from the technology. For example, electrical signals described herein can be delivered at combinations of parameter values within the foregoing ranges at values that are not expressly disclosed herein. Certain aspects of the technology described in the context of particular embodiments may be combined or eliminated in other embodiments. Further, while advantages associated with certain embodiments of the disclosed technology have been described in the context of those embodiments, other embodiments may also exhibit such advantages, and not all embodiments need necessarily exhibit such advantages to fall within the scope of the present technology. Accordingly, the disclosure and associated technology can encompass other embodiments not expressly shown or described herein.

[0081] The use of “and / or,” as in “A and / or B” refers to A alone, B alone, and both A and B. Additionally, the term “comprising” is used throughout to mean including atleast the recited feature(s) such that any greater number of the same feature and / or additional types of other features are not precluded. It will also be appreciated that specific embodiments have been described herein for purposes of illustration, but that various modifications may be made without deviating from the technology. Further, while advantages associated with certain embodiments of the technology have been described in the context of those embodiments, other embodiments may also exhibit such advantages, and not all embodiments need necessarily exhibit such advantages to fall within the scope of the technology. Accordingly, the disclosure and associated technology can encompass other embodiments not expressly shown or described herein.

[0082] Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, to between the upper and lower limits of that range is also specifically disclosed. Each smaller range between any stated value or intervening value in a stated range and any other stated or intervening value in that stated range is encompassed within the disclosure. The upper and lower limits of these smaller ranges may independently be included or excluded in the range, and each range where either, neither or both limits are included in the smaller ranges is also encompassed within the disclosure, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the disclosure.

Claims

CLAIMSI / We claim:1 . A method of treating inflammatory bowel disease (IBD) in a patient using sacral nerve stimulation (SNS) treatment, the method comprising: providing a swallowable capsule to the patient, the swallowable capsule carrying at least one sensor for measuring one or more physiologic parameters associated with a Gl tract of the patient, after the patient has swallowed the swallowable capsule, measuring the one or more physiologic parameters using the sensor; and controlling the SNS treatment based at least in part on the measured physiologic parameters, wherein controlling the SNS treatment includes at least one of initiating a stimulation session, ceasing a stimulation session, or adjusting one or more stimulation parameters of the SNS treatment.

2. The method of claim 1 wherein controlling the SNS treatment includes adjusting one or more stimulation parameters, and wherein the one or more stimulation parameters include at least one of amplitude, frequency, pulse width, duty cycle, and / or electrode combination.

3. The method of claim 1 wherein controlling the SNS treatment includes initiating a stimulation session based at least in part on the measured physiologic parameter.

4. The method of claim 1 wherein the one or more physiologic parameters include one or more of: (i) a presence or absence of blood in the Gl tract, (ii) a temperature of the Gl tract, (iii) a peristaltic wave frequency, strength, and / or timing, (iv) a pH of gut contents throughout the Gl tract, (v) gas molecules in the gut, (vi) enzymes and / or cytokines in the gut, (vii) electrical activity of the gut, (viii) sounds within the gut, (ix) gut motility, (x) images of portions of the Gl tract, (xi) videos of portions of the Gl tract.

5. The method of claim 1 wherein measuring the one or more physiologic parameters using the swallowable capsule further includes measuring a select portion of the Gl tract.

6. The method of claim 5 wherein the swallowable capsule is programmed to begin measuring the one or more physiological measurements after a predetermined time has elapsed since the patient swallowed the capsule.

7. The method of claim 5 wherein the swallowable capsule includes a dissolvable coating configured to dissolve after exposure to certain bodily fluids to expose the at least one sensor.

8. The method of claim 1 , further comprising: correlating the one or more measured physiologic parameters with one or more stimulation parameters and with one or more patient states; and generating a predictive model based on the correlation between the measured physiologic parameters and the one or more stimulation parameters, and based on the correlation between the measured physiologic parameters and the one or more patient states; wherein controlling the SNS treatment further includes controlling the SNS treatment at least in part on an output of the predictive model.

9. The method of claim 8, further comprising: continuously or periodically updating the predictive model based on additional physiologic parameter measurements and additional patient states.

10. A method of treating inflammatory bowel disease (IBD) in a patient using sacral nerve stimulation (SNS) treatment, the method comprising: providing a swallowable capsule having at least one sensor configured to measure one or more physiologic parameters associated with a Gl tract of the patient; and programming a sacral nerve stimulation system to control delivery of electrical stimulation to a sacral nerve of the patient based at least in part on theone or more physiologic parameters measured by the swallowable capsule.1 1 . The method of claim 10 wherein programming the sacral nerve stimulation system includes programming the system to automatically initiate a stimulation session in response to the one more physiologic parameters meeting a predetermined threshold.

12. The method of claim 10 wherein programming the sacral nerve stimulation system includes programming the system to automatically terminate a stimulation session in response to the one or more physiologic parameters meeting a predetermined threshold.

13. The method of claim 10 wherein programming the sacral nerve stimulation system includes programming the system to automatically adjust a stimulation parameter of the electrical stimulation based on the one or more physiologic parameters.

14. The method of claim 10 wherein the one or more physiologic parameters include one or more of: (i) a presence or absence of blood in the Gl tract, (ii) a temperature of the Gl tract, (iii) a peristaltic wave frequency, strength, and / or timing, (iv) a pH of gut contents throughout the Gl tract, (v) gas molecules in the gut, (vi) enzymes and / or cytokines in the gut, (vii) electrical activity of the gut, (viii) sounds within the gut, (ix) gut motility, (x) images of portions of the Gl tract, (xi) videos of portions of the Gl tract.

15. The method of claim 10 wherein the swallowable pill is configured to measure the one or more physiologic parameters at one or more select portions of a Gl tract of the patient.

16. The method of claim 15 wherein the swallowable pill is configured to measure the one or more physiologic parameters at one or more predetermined time intervals.

17. The method of claim 15 wherein the swallowable pill includes a dissolvable coating configured to dissolve upon exposure to bodily fluids within the Gl tract to expose the at least one sensor.

18. A system for treating inflammatory bowel disease (IBD) in a patient, the system comprising: an implantable signal delivery element positionable proximate a sacral nerve of the patient; a signal generator programmed with first instructions that, when executed, cause the signal generator to generate and deliver an electrical signal to the sacral nerve of the patient via the implantable signal delivery element; and a controller for controlling the signal generator, wherein the controller is programmed with second instructions that, when executed, cause the controller to — receive one or more measured physiologic parameters collected from a swallowable pill ingestible by the patient and having at least one sensor; and based on the one or more measured physiologic parameters collected from the swallowable pill, control the signal generator to initiate a stimulation session, cease a stimulation session, or adjust one or more stimulation parameters of the electrical signal.

19. The system of claim 18, further comprising the swallowable pill.

20. The system of claim 19 wherein the swallowable pill is configured to measure the one or more physiologic parameters at one or more predetermined locations along a Gl tract of the patient.

21. The system of claim 19 wherein the swallowable pill is programmed to automatically measure the one or more physiologic parameters at one or more predetermined time intervals.

22. The system of claim 19 wherein the swallowable pill includes a dissolvable coating configured to dissolve upon exposure to bodily fluids within the Gl tract of the patient to expose the at least one sensor.

23. The system of claim 18 wherein the one or more physiologic parameters include one or more of: (i) a presence or absence of blood in the Gl tract, (ii) a temperature of the Gl tract, (Hi) a peristaltic wave frequency, strength, and / or timing, (iv) a pH of gut contents throughout the Gl tract, (v) gas molecules in the gut, (vi) enzymes and / or cytokines in the gut, (vii) electrical activity of the gut, (viii) sounds within the gut, (ix) gut motility, (x) images of portions of the Gl tract, (xi) videos of portions of the Gl tract.

24. The system of claim 18 wherein the second instructions cause the controller to direct the signal generator to initiate a stimulation session in response to the one or more measured physiologic parameters meeting a predetermined threshold.

25. The system of claim 18 wherein the second instructions cause the controller to direct the signal generator to terminate a stimulation session in response to the one or more measured physiologic parameters meeting a predetermined threshold.

26. The system of claim 18 wherein the second instructions cause the controller to direct the signal generator to adjust a stimulation parameter of the electrical signal based on the one or more measured physiologic parameters.

27. The system of claim 18 wherein the operation of receiving the one or more measured physiologic parameters collected from the swallowable pill includes receiving the one or more measured physiologic parameters directly from the swallowable pill.

28. The system of claim 18 wherein the operation of receiving the one or more measured physiologic parameters collected from the swallowable pill includes receiving the one or more measured physiologic parameters from a computing system distinct from the swallowable pill.

29. A system for treating inflammatory bowel disease (IBD), the system comprising: a processor; and a non-transitory computer-readable medium storing a predictive model and instructions that, when executed by the processor, cause the system to: receive first treatment data from at least one patient receiving sacral nerve stimulation for treating IBD, wherein the first treatment data includes one or more first measured physiologic parameters and at least one of a patient state or a patient stimulation parameter, establish a correlation between the one or more first measured physiologic parameters and the patient state and / or the patient stimulation parameter, and update the predictive model based on the correlation between the one or more first measured physiologic parameters and the patient state and / or the patient stimulation parameter, wherein the predictive model is configured to predict an onset of a symptomatic episode associated with the patient’s IBD and / or recommend a particular therapy parameter for treating the patient’s IBD, based on second treatment data that includes one or more second measured physiologic parameters collected at a different point in time than the first treatment data.

30. The system of claim 29 wherein the first treatment data includes the patient state.31 . The system of claim 30 wherein the patient state includes an indication of a symptomatic episode.

32. The system of claim 29 wherein the first treatment data includes the patient stimulation parameter.

33. The system of claim 32 wherein the patient stimulation parameter includes an amplitude, frequency, pulse width, and / or electrode combination of the sacral nerve stimulation.

34. The system of claim 29 wherein the first treatment data includes both the patient state and the patient stimulation parameter, and wherein the operation of establishing a correlation includes establishing a correlation between each of the one or more first measured physiologic parameters, the patient state, and the patient stimulation parameter.

35. The system of claim 29 wherein the predictive model is configured to predict the onset of a symptomatic episode associated with the patient’s IBD based on the second treatment data.

36. The system of claim 29 wherein the predictive model is configured to recommend the particular therapy parameter for treating the patient’s IBD based on the second treatment data.

37. The system of claim 29 wherein the predictive model is configured to both predict the onset of a symptomatic episode for the patient and to recommend the particular therapy parameter for the patient based on the second treatment data.

38. The system of claim 29 wherein the predictive model includes an artificial intelligence and / or machine learning model.

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