Clinical trial NCT04428619: Percutaneous Electrical Nerve Field Stimulation for Adults With Irritable Bowel Syndrome
Official title: Neuromodulation With Percutaneous Electrical Nerve Field Stimulation for Adults With Irritable Bowel Syndrome: A Randomized, Double-Blind, Sham-Controlled Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Irritable Bowel Syndrome
Abdominal Pain
Autonomic Nervous System Imbalance
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
Collaborators: name: Innovative Health Solutions
First posted: 2020-06-11
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 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)

Primary outcomes:
measure: Mean Change in IBS Symptom Severity From Baseline
timeFrame: 4 weeks, 8 weeks.
Secondary outcomes:
measure: Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at 4 Weeks.
timeFrame: 4 weeks
measure: IBS Symptom Severity Responder Rate
timeFrame: Week 4
measure: Mean Change in Average Daily Worst Abdominal Pain From Baseline
timeFrame: Week 4
measure: Change in Average Daily Stool Consistency From Baseline
timeFrame: Week 4
measure: Change in Average Weekly Bowel Habits From Baseline
timeFrame: Week 4, week 8
measure: Change in Quality of Life From Baseline
timeFrame: Week 4, week 8
measure: "Number of Participants With Treatment-related Adverse Events as Assessed by a Weekly Adverse Events Questionnaire
timeFrame: Week 4
measure: Change in Average Weekly Bloating Symptoms From Baseline
timeFrame: 4 weeks, 8 weeks
measure: Change in Average Weekly Abdominal Pain Symptoms From Baseline
timeFrame: 4 weeks, 8 weeks
measure: Chang in Average Weekly Bowel Habits From Baseline
timeFrame: 4 weeks, 8 weeks
measure: Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at Baseline.
timeFrame: Baseline
measure: Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at Baseline.
timeFrame: Baseline
measure: Mean and Standard Deviation of Heart Rate Variability (HRV) Measures in PENFS Device and Sham Groups at 4 Weeks.
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA
state: California
Study officials:
affiliation: University of California, Los Angeles
name: Lin Chang, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kovacic K, Hainsworth K, Sood M, Chelimsky G, Unteutsch R, Nugent M, Simpson P, Miranda A. Neurostimulation for abdominal pain-related functional gastrointestinal disorders in adolescents: a randomised, double-blind, sham-controlled trial. Lancet Gastroenterol Hepatol. 2017 Oct;2(10):727-737. doi: 10.1016/S2468-1253(17)30253-4. Epub 2017 Aug 18.
citation: Krasaelap A, Sood MR, Li BUK, Unteutsch R, Yan K, Nugent M, Simpson P, Kovacic K. Efficacy of Auricular Neurostimulation in Adolescents With Irritable Bowel Syndrome in a Randomized, Double-Blind Trial. Clin Gastroenterol Hepatol. 2020 Aug;18(9):1987-1994.e2. doi: 10.1016/j.cgh.2019.10.012. Epub 2019 Oct 14.