A Randomized, Single Centre, Double-blind, Parallel, Sham-controlled Pilot Study Using gammaCore®-G

Study Overview
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Brief Summary
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A randomized, sham-controlled, single-centre pilot investigation designed to compare two parallel groups, gammaCore®-G (active treatment) and a sham, (inactive) treatment in subjects with FGIDs.

Detailed Description
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This study, in subjects with FGIDs, is a , randomized, sham-controlled, single-centre pilot investigation designed to compare two parallel groups, gammaCore®-G (active treatment) and a sham, (inactive) treatment. The study period will begin with a two-week run-in period, followed by a four week comparative period when the subjects will randomized (1:1) to either active treatment or sham (inactive) treatment. The comparative period will be followed by an open label four week period, where the subjects in the sham treatment group will switch in treatment assignment to receive active treatment and the active group will continue to receive an active treatment.

Official Title
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A Randomized, Single Centre, Double-blind, Parallel, Sham-controlled Pilot Study of the gammaCore®-G, a Non-invasive Vagus Nerve Stimulator Device for Treatment of Symptoms Caused by Functional Dyspepsia or Irritable Bowel Syndrome

Conditions
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Dyspepsia, Irritable Bowel Syndrome

Intervention / Treatment
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* Device: gammaCore®-G


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subjects have to meet all of the following criteria to be eligible to enter the investigation: Signed Informed Consent Form Age >18 Diagnose with FD or IB Rome III criteria Is able to complete the diary, use the device and to follow study procedures Dyspepsia inclusion criteria, functional dyspepsia according to Rome III Diagnostic Criteria for Functional Gastrointestinal Disorders, one or more of the following: Bothersome postprandial fullness Early satiation Epigastric pain Epigastric burning No evidence of structural disease (including at upper endoscopy) that is likely to explain the symptoms * Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis IBS inclusion criteria, Irritable Bowel Syndrome* according to Rome III Diagnostic Criteria for Functional Gastrointestinal Disorders Recurrent abdominal pain or discomfort** at least 3 days/month in the previous 3 months associated with two or more of the following: Improvement with defecation Onset associated with a change in frequency of stool Onset associated with a change in form (appearance) of stool Criterion fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis ** Discomfort means an uncomfortable sensation not described as pain. In pathophysiology research and clinical trials, a pain/discomfort frequency of at least 2 days a week during screening evaluation is recommended for subject eligibility. Exclusion Criteria: Subjects meeting any of the following criteria will not be permitted to enter the investigation: Any positive endoscopic findings such as abnormal biopsy findings and/or any other abnormal finding judged by the Investigator Any positive findings after sigmoidoscopy or colonoscopy such as diverticulosis, inflammatory bowel disease or other abnormal finding judged by the Investigator. Vagotomy at any location Has a neck lesion (including lymphadenopathy), dysaesthesia, previous surgery or abnormal anatomy at the site gammaCore®-G treatment Has known or suspected severe atherosclerotic cardiovascular disease, severe carotid artery disease (e.g. bruits or history of transient ischemic attack (TIA) or cerebral vascular accident CVA), congestive heart failure (CHF), known severe coronary artery disease or recent (5 years) myocardial infarction Has an abnormal baseline ECG (e.g. second and third degree heart block, atrial fibrillation, atrial flutter, recent history of ventricular tachycardia or ventricular fibrillation, or clinically significant premature ventricular contraction Has uncontrolled hypertension Is currently implanted with an electrical and/or neurostimulator device, including but not limited to cardiac pacemaker or defibrillator, vagal neurostimulator, deep brain stimulator, spinal stimulator, bone growth stimulator, gastric stimulator or cochlear implant Has a history of carotid endarterectomy or vascular neck surgery Has been implanted with metal cervical spine hardware or has a metallic implant near the GammaCore®-G stimulation site Has a recent (within 12 months) or repeated history of syncope Has a recent (within 12 months) or repeated history of seizures Has psychiatric or cognitive disorder and/or behavioural problems which in the opinion of the clinician may interfere with the study Is pregnant, nursing, thinking of becoming pregnant during the study period Is participating in any other therapeutic clinical investigation or has participated in a clinical trial within 30 days period prior to this study Is a relative of or an employee of the investigator or the clinical study site Used gammaCore®-G previously

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: gammaCore®-G<br>The user/operator applies the gammaCore®-G device to the skin on the right side and left side of the neck. The 2 stimulations should be performed on the same side of the neck before stimulating the other side. This is also applies with the doses increase in the open label phase. The user applies conductive gel to the stimulation surfaces to maintain an uninterrupted conductive path from the stimulation surfaces to the skin. The device is capable of delivering multiple patient treatments (doses). Each dose consists of 90 seconds of stimulation; for each dose, the device is active for 120 seconds before automatically stopping stimulation.The extra 30 seconds allows . | Device: gammaCore®-G<br>* The gammaCore®-G device is a reusable, hand-held, portable device consisting of two 3.0 VDC batteries (not replaceable or user serviceable), signal generating and amplifying electronics, and two buttons for operator control of the signal amplitude. The device provides visible (light display) and audible feedback on device and stimulation status<br>|
| Sham Comparator: gammaCore®-G sham<br>The sham device is a hand-held portable device that appears identical to the gammaCore®-G, in look, weight, visual and audible feedback, user application and control. It passes a low frequency (0.1 Hz) biphasic DC signal into the tissue, which can be felt as a tingling sensation but does not stimulate the vagus nerve or cause muscle contraction. Similar to the active device, the sensation becomes more pronounced as the amplitude is increased, until it is uncomfortable, at which point the amplitude is decreased slightly until tolerable. Like the active device, the sham device is a multi-use device capable programmed to deliver up to 150, 90-second treatments with a 30-second margin for set-up and operator adjustment of the stimulation intensity. | Device: gammaCore®-G<br>* The gammaCore®-G device is a reusable, hand-held, portable device consisting of two 3.0 VDC batteries (not replaceable or user serviceable), signal generating and amplifying electronics, and two buttons for operator control of the signal amplitude. The device provides visible (light display) and audible feedback on device and stimulation status<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptom Changes in Subjects With Functional Gastrointestinal Disorder (Functional Dyspepsia and Irritable Bowel Syndrome) | Global Overall Symptom (GOS) scale is self-reported. Patients grade overall severity of dyspepsia symptoms over a retrospective period of time. The scale uses a 7-point Likert scale ranging from minimum 1 = no problem to maximum 7 = very severe problem. Subjects assess how their stomach problems have been over the specific time period, and indicate severity of symptoms for 10 specific upper GI symptoms (epigastric pain, epigastric discomfort, heartburn, acid regurgitation, upper abdominal bloating, excessive belching, nausea, early satiety, postprandial fullness, other epigastric symptoms). Total minimum = 10 and total maximum = 70. The Irritable Bowel Syndrome Score (IBS) measures severity of symptoms by 5 questions: abdominal pain, number days with pain in every 10 days (multiplied by 10), abdominal distension, bowel movement satisfaction, interference with general life. Each question scores from 0 (not severe) to 100 (severe). Total score: Min = 0 healthy; Max = 500 severely sick. | Last 2 weeks in the 4 week Randomized period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life (QoL) Using the Functional Digestive Disorder Quality of Life (FDDQL) | Compare Quality of Life in last 2 weeks in the randomized period with the run-in period, and compare of Quality of life in the open label period to randomization period using the Functional Digestive Disorder Quality of Life (FDDQL) questionnaire. The Functional Digestive Disorder Quality of Life (FDDQL) questionnaire is designed to measure Quality of Like (QOL) in patients with Functional Dyspepsia (FD) or Irritable Bowel Syndrome (IBS). The questionnaire is composed of 43 items (questions) investigating 8 dimensions: Daily activities, Anxiety, Diet, Sleep, Discomfort, Health, Coping and Stress. For the 43 items, patients rate the impact of their condition over the 8 dimensions from 1-5, where 1 = Not at all, 2 = A little Bit, 3 = Moderately, 4= Quite a bit, and 5 = Extremely. The mean score of the 8 dimensions is shown in the outcome measure data table. | Run-In (2 weeks), Randomized (4 weeks) and Open Label (4 weeks) period | 
| Change in Frequency of Symptoms Using the Short-Form Leeds Dyspepsia Questionnaire (SFLDQ) | Compare last 2 weeks in randomized period with the run-in period; & compare open label period to randomization period using Short-Form Dyspepsia Questionnaire (SFLDQ).The SFLDQ is a validated, self-completed questionnaire that measures frequency and severity of dyspepsia. The questionnaire comprises of 5 questions, questions 1 to 4 are about the patients dyspeptic symptoms and question 5 is about the most troublesome symptom for the patient. Questions 1 to 4 comprise of two stems concerning 'frequency' (how often the subject has the symptom over the last 2 months) and 'severity' (how often has this symptom interfered with normal activities over the last 2 months). Subjects choose from: Not at all, less than monthly, between monthly & weekly, between weekly & daily, more than daily or no response. In question 5 the subject reports which symptoms has been most troublesome for each of the study periods. Results for Question 5 of the SFLDQ are reported separately in outcome measure 7. | Run-In (2 weeks), Randomized (4 weeks) and Open Label (4 weeks) period | 
| Use of Concomitant Medication (Intake and Dose) During the Course of the Study | Compare last 2 weeks in randomised period with the run-in period, comparison open label period to randomization period. Concomitant medications were recorded and the number of subjects taking one or more concomitant medications is compared in the active and shams groups for both Functional Dyspepsia and Irritable Bowel Syndrome cohorts during the run-in, randomized and open label periods. | Run-In (2 weeks) and Randomized (4 weeks) | 
| Symptom Change at 8 Weeks Compared to 4 Weeks (GOS Dyspepsia or IBS Severity Scoring System) | Global Overall Symptom (GOS) scale is self-reported. Patients grade overall severity of dyspepsia symptoms over a retrospective period of time. The scale uses a 7-point Likert scale ranging from minimum 1 = no problem to maximum 7 = very severe problem. Subjects assess how their stomach problems have been over the specific time period, and indicate severity of symptoms for 10 specific upper GI symptoms (epigastric pain, epigastric discomfort, heartburn, acid regurgitation, upper abdominal bloating, excessive belching, nausea, early satiety, postprandial fullness, other epigastric symptoms). Total minimum = 10 and total maximum = 70. The Irritable Bowel Syndrome Score (IBS) measures severity of symptoms by 5 questions: abdominal pain, number days with pain in every 10 days (multiplied by 10), abdominal distension, bowel movement satisfaction, interference with general life. Each question scores from 0 (not severe) to 100 (severe). Total score: Min = 0 healthy; Max = 500 severely sick. | Run-In (2 weeks), Randomized (4 weeks) and Open Label (4 weeks) period | 
| Number of Participants With Adverse Events | Summary of Treatment Emergent Adverse Events. Subjects were monitored for occurrence of adverse events from the start of the run-in period to the end of the open label period.. | Run-In (2 weeks), Randomized (4 weeks) and Open Label (4 weeks) period | 
| Change in Frequency of Symptoms Using the Short-Form Leeds Dyspepsia Questionnaire (SFLDQ) | Short-Form Leeds Dyspepsia Questionnaire (SFLDQ): Question 5: Most Troublesome Symptom. In question five of the SFLDQ the subject reports which of the symptoms has been most troublesome to them, this is also reported for each of the study periods. (Note: results of questions 1-4 of the SFLDQ are reported separately in outcome measure 3.) | Run-In (2 weeks), Randomized (4 weeks) and Open Label (4 weeks) period |