Percutaneous Electrical Nerve Field Stimulation for Adults With Irritable Bowel Syndrome

Not Applicable

Recruiting

• Conditions: Autonomic Nervous System Imbalance; Irritable Bowel Syndrome; Abdominal Pain
• Interventions: Device: Peripheral Electrical Nerve Field Stimulation (PENFS) Device; Device: Sham Device

• Registration Number: NCT04428619
• Lead Sponsor: University of California, Los Angeles

Brief Summary

This is a prospective, double-blind, randomized, sham-controlled pilot study evaluating the efficacy of percutaneous electrical nerve field stimulation for the treatment of adult patients with irritable bowel syndrome (IBS).

Detailed Description

IBS has a worldwide prevalence around 11% and is characterized by chronic or recurrent abdominal pain associated with altered bowel habits. Abnormalities within the brain-gut axis, visceral hypersensitivity, and dysfunction of the autonomic nervous system are important components contributing to the pathophysiology of IBS. Despite recent advances in medical therapies for IBS, a significant subgroup of patients fails to experience satisfactory relief of abdominal pain. Given evidence of anti-inflammatory and anti-nociceptive components of vagal nerve pathways, peripheral field stimulation of the vagus nerve may help reduce abdominal pain in patients with IBS.

Percutaneous electrical nerve field stimulation (PENFS) administered via the IB-Stim device (Innovative Health Solutions, Versailles, IN, USA) has been shown to be efficacious in adolescent patients with abdominal-pain-related functional GI disorders, including IBS. This device uses discontinuous frequencies of stimulation to target central pain pathways through branches of cranial nerves V, VII, IX, and X that innervate the external ear and project to certain brainstem nuclei, including the nucleus tractus solitarius (NTS). The NTS then acts as a relay station to other brain areas involved in pain modulation and autonomic control, including the rostral ventral medulla, locus coeruleus, hypothalamus, and amygdala. In adolescent studies, PENFS was associated with a greater reduction in worst abdominal pain and composite abdominal pain scores from baseline as well as compared with a sham device after three weeks of treatment. These effects were sustained over an extended follow-up period with minimal to no side effects. In addition, a greater proportion of adolescents in the PENFS arm achieved at least a 30% reduction in worst abdominal pain scores from baseline after 3 weeks of treatment.

The IB-Stim is the first device to be approved by the Food and Drug Administration (FDA) for the treatment of functional abdominal pain in adolescents aged 11-18 with IBS. However, the efficacy of PENFS in adults with IBS is not currently known. This study is a double-blind, randomized, sham-controlled pilot study evaluating the efficacy of PENFS using IB-Stim for the treatment of IBS symptoms in adult patients with IBS.

Study Timeline

• Study First Submitted: 2020-05-28
• Study First Submitted QC: 2020-06-09
• Study First Posted: 2020-06-11
• Study Start: 2020-08-01
• Status Verified: 2023-01
• Last Update Submitted: 2023-01-09
• Last Update Posted: 2023-01-11
• Primary Completion: 2024-05-01
• Study Completion: 2024-11-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 54

Inclusion Criteria

• Adults, aged 18-60 years, who are able to provide written, informed consent.
• Patients must meet Rome IV criteria for IBS, confirmed by a gastroenterologist who specializes in functional GI disorders. Any of the IBS bowel habit subtypes (diarrhea, constipation, mixed bowel habits, unclassified) will be allowed.
• Average daily worst abdominal pain score between 4 and 8 (on a 0-10-point rating scale).
• Minimum of 2 days of abdominal pain/week prior to starting trial.
• At least moderate IBS symptom severity with an IBS-SSS of at least 175 (total score range 0-500).
• If receiving pharmacologic therapy for abdominal pain associated with IBS, doses must be stable for at least 60 days prior to enrollment in the trial.
• If receiving pharmacologic therapy for IBS that does not have an effect on abdominal pain, doses must be stable for at least 30 days prior to enrollment in the trial.

Mandatory

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Exclusion Criteria

• Patients under the age of 18 years or over the age of 60 years
• Patients who cannot provide informed consent or do not speak English
• Co-morbid, organic medical conditions associated with abdominal pain, including: Inflammatory bowel disease, chronic liver disease, peptic ulcer disease, celiac disease, diverticulitis, appendicitis, colorectal cancer, endometriosis, pregnancy, other intestinal or extra-intestinal malignancies. Patients with overlapping functional GI disorders (i.e. functional dyspepsia) will not be excluded as long as IBS is their predominant disorder
• History of surgery involving CN V, VII, IX, or X.
• History of abdominal surgeries other than appendectomy or cholecystectomy at least 6 months before entry into trial.
• Patients on chronic opioids, benzodiazepines, or with illicit substance use
• Patients with underlying neurologic conditions, including history of: seizures, CVA, uncontrolled migraines, traumatic brain injury, multiple sclerosis
• Patients with underlying psychiatric conditions
• Patients with dermatologic conditions affecting the ear, face, or neck region (i.e. psoriasis), or with cuts or abrasions to the external ear that would interfere with needle placement
• Patients with hemophilia or other bleeding disorders
• Patients with any implanted electrical device
• Patients who are pregnant or breastfeeding

Preferred, but not mandatory, exclusion criteria:

• Movement disorder
• Unwillingness to wear the SmartWatch on upper extremity (left or right wrist)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Peripheral Electrical Nerve Field Stimulation (PENFS) Device	Peripheral Electrical Nerve Field Stimulation (PENFS) Device	The PENFS device has a battery activated generator and wire harness. Four leads are attached to the generator, each with a sterile 2 mm, titanium needle. The patient's ear is trans-illuminated to identify neurovascular bundles that are avoided during needle placement. The generator is attached with adhesive to the skin behind the patient's ear. Needles are inserted into the dorsal and ventral aspects of the ear, within 1-1.5 mm of the vascular branches to create a field effect. The device settings are standardized and deliver 3.2 volts with alternating frequencies (1 ms pulses of 1 Hz and 10 Hz) every 2 s. This stimulation targets central pain pathways through branches of cranial nerves V, VII, IX, and X, which innervate the external ear. The device is worn for 5 days/week for a total of 4 weeks. Patients remove devices at home on day 6 of each treatment cycle. Patients will be asked to wear a SmartWatch during the study to monitor heart rate.
Sham Device	Sham Device	The sham devices will be identical to the active devices but will not administer electrical charges. Per manufacturer design and patient anecdotal experience from previous studies, both active stimulation and sham are below detectable sensation threshold. Per report from previous studies, some patients may experience a sensation around the ear after percutaneous needle placement; however, this sensation can occur with equal likelihood in the active or sham device. The device is worn for 5 days a week for a total of 4 weeks. Patients remove devices at home on day 6 of each treatment cycle. Patients will also be asked to wear a SmartWatch as above.

Primary Outcome Measures

Name	Time	Method
Mean change in IBS symptom severity from baseline	Week 4	To compare the efficacy of PENFS therapy versus sham therapy on the change in IBS symptom severity in adult IBS patients after 4 weeks of treatment, assessed through a mean change in the IBS-SSS.

Secondary Outcome Measures

Name	Time	Method
Change in average weekly abdominal pain symptoms from baseline	Week 4, week 8	To compare the efficacy of PENFS therapy versus sham therapy on the change in average weekly abdominal pain symptoms after 4 weeks of treatment and at extended follow-up (8 weeks) compared to baseline, assessed through the PROMIS Gastrointestinal Belly Pain Scale (percentiles 2-100%; higher percentiles indicate worse abdominal pain).
Change in average weekly bowel habits from baseline	Week 4, week 8	To compare the efficacy of PENFS therapy versus sham therapy on the change in average weekly bowel habits after 4 weeks of treatment and at extended follow-up (8 weeks) compared to baseline, assessed through the PROMIS Gastrointestinal Constipation Scale (percentiles 0.3-100%; higher percentiles indicate greater constipation) and Gastrointestinal Diarrhea Scale (percentiles 1-100%; higher percentiles indicate greater diarrhea).
Mean change in IBS symptom severity from baseline	Week 8	To compare the efficacy of PENFS therapy versus sham therapy on the change in IBS symptom severity in adult IBS patients at extended follow-up (8 weeks), assessed through a mean change in the IBS-SSS.
IBS symptom severity responder rate	Week 4	To compare the efficacy of PENFS therapy versus sham therapy on the change in IBS symptom severity in adult IBS patients after 4 weeks of treatment compared to baseline. Participants will be considered responders if there is at least a 50-point reduction on the IBS-SSS.
Mean change in average daily worst abdominal pain from baseline	Week 4	To compare the efficacy of PENFS therapy versus sham therapy on mean worst daily abdominal pain scores after 4 weeks compared to baseline in adult patients with IBS
Change in quality of life from baseline	Week 4, week 8	To compare the efficacy of PENFS therapy versus sham therapy on the change in IBS-quality of life (IBS-QOL) in adult patients with IBS after 4 weeks of treatment and at extended follow-up (8 weeks) compared to baseline. IBS QOL will be assessed on a scale from 0-100, with higher scores indicating better IBS specific quality of life.
Change in heart rate variability from baseline	Week 4	To compare the change in resting cardio-autonomic tone, i.e. heart rate variability (HRV), at baseline and after 4 weeks of treatment in responders vs. non-responders in adult patients with IBS.
Daily worst abdominal pain responder rate	Week 4	To compare the proportion of adult patients with IBS who experience a change of ≥ 30% from baseline in average daily worst abdominal pain scores after 4 weeks of treatment (measured using a validated, 11-point numeric rating scale). Participants who have a reduction in daily worst abdominal pain scores of ≥ 30% from baseline will be considered clinical responders.
Change in average daily stool consistency from baseline	Week 4	To compare the efficacy of PENFS therapy versus sham therapy on the change in average daily stool consistency after 4 weeks of treatment compared to baseline, assessed using the Bristol Stool Form Scale (BSFS) (stool types 1-7; types 1 and 2 indicate constipation, types 3 and 4 are normal consistency stools, type 5 indicates stool lacking fiber, types 6 and 7 indicate diarrhea).
Change in average weekly bloating symptoms from baseline	Week 4, week 8	To compare the efficacy of PENFS therapy versus sham therapy on the change in average weekly bloating symptoms after 4 weeks of treatment and at extended follow-up (8 weeks) compared to baseline, assessed through the PROMIS Gastrointestinal Gas and Bloating Scale (percentiles 0.1-100%; higher percentiles indicate greater gas and bloating).
Incidence of treatment-related adverse events as assessed by a weekly adverse events questionnaire	Week 4	To compare the incidence of treatment-related adverse events from PENFS therapy versus sham therapy in adult patients with IBS. Adverse events will be assessed by a weekly adverse events questionnaire that determines the severity of the adverse event, the relationship to the study intervention, the action taken regarding the study intervention, the outcome of the adverse event, whether or not the adverse event was expected, and if the event was considered a serious adverse event (SAE).

Trial Locations

Locations (1)

UCLA; 🇺🇸 Los Angeles, California, United States