RCT of Gut-directed Hypnotherapy in Ehlers-Danlos Syndromes and Generalized Hypermobility Spectrum Disorders

A Randomized Controlled Trial of Gut-directed Hypnotherapy for Treatment of Irritable Bowel Syndrome in Ehlers-Danlos Syndromes and Generalized Hypermobility Spectrum Disorders

This randomized, controlled trial (RCT) will evaluate the effectiveness of gut-directed hypnotherapy for management of Irritable Bowel Syndrome (IBS) in individuals diagnosed with Ehlers-Danlos Syndromes or Generalized Hypermobility Spectrum Disorders (G-HSD). Consenting patients recruited from the Toronto General Hospital GoodHope Ehlers-Danlos Syndrome Clinic will be randomly assigned to one of two groups: (1) standard medical therapy or (2) standard medical therapy plus eight sessions of gut-directed hypnotherapy. The main questions this study will answer are:

1. Is gut-directed hypnotherapy an efficacious treatment for IBS symptoms among individuals with EDS or G-HSD?
2. Does gut-directed hypnotherapy improve other gut symptoms, quality of life, visceral sensitivity, and emotional distress?
3. Is the activity of the parasympathetic nervous system (i.e. the body's "rest and digest" system) associated with IBS symptoms or treatment outcomes among individuals with EDS or G-HSD?

All participants will be asked to meet with a gastroenterologist three times as part of the standard medical therapy. At each physician visit, they will undergo electrocardiogram recording and complete self-report measures of gastrointestinal symptoms, quality of life, visceral sensitivity, and emotional distress. Participants randomized to receive gut-directed hypnotherapy will also eight weekly remotely-delivered sessions of gut-directed hypnotherapy delivered by a trained behavioral therapist in between the first and second physician visit. At each session of gut-directed hypnotherapy, a voluntary, pleasant, and dream-like state of deep relaxation will be induced and suggestions made for greater relaxation, abdominal comfort, and normalization of gut function. The first session will also include 30 minutes of education on the nature of the gut-brain axis and hypnotherapy prior to hypnosis.

Researchers will compare study groups to see if participants who engaged in gut-directed hypnotherapy had greater improvement in IBS symptoms, other gastrointestinal symptoms, quality of life, visceral sensitivity, and emotional distress. Exploratory analyses will examine the relationships among heart rate variability, an index of parasympathetic nervous system activity, and study outcomes.

Study Overview

• Status: Not yet recruiting
• Conditions: Irritable Bowel Syndrome; Gastrointestinal Dysfunction; Ehlers-Danlos Syndrome; Hypermobility Syndrome
• Intervention / Treatment: Other: Standard Medical Therapy; Behavioral: Gut-directed hypnotherapy

• Study Type: Interventional
• Enrollment (Estimated): 74
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Misbah Salim Salim; Phone Number: 7887 4166035800; Email: misbah.salim@uhn.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Physician diagnosis of Ehlers-Danlos Syndrome or Generalized Hypermobility Spectrum Disorder
• Physician diagnosis of Irritable Bowel Syndrome according to the Rome IV criteria.
• If receiving pharmacologic therapy for IBS, they must be on a stable dose for 4 weeks prior to study enrollment

Exclusion Criteria:

• Patients with diagnosed lower bowel disease (e.g. inflammatory bowel disease, celiac's disease)
• Patients with history of major gastrointestinal surgery (except appendectomy and/or cholecystectomy > 6 months prior to enrollment)
• Patients with limited comprehension of English or hearing difficulty who would not be able to understand the verbal instructions for clinical hypnosis
• Patients with a known history of serious mental illness (e.g., schizophrenia, dissociative identity disorder)
• Patients with cognitive deficits whose comprehension may limit benefit
• Patients with heavy alcohol use (> 15 drinks/week for men, > 10 drinks/week for women)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Standard Medical Therapy; Standard Medical Treatment will be administered by board certified gastroenterologists through the EDS Clinic gastroenterology clinical care pathway. Therapies will be individualized to the participants' current symptoms and severity of symptoms as per current clinical guidelines for management of IBS. Potential therapies that may be administered include dietary changes, supplemental fibre, and pharmacotherapy (including neuromodulators) as appropriate.	Other: Standard Medical Therapy; Standard medical treatment will be administered by board certified gastroenterologists
Experimental: Standard Medical Therapy plus Gut-Directed Hypnotherapy; In addition to Standard Medical Therapy, participants randomized to this arm will attend 8 sessions of gut-directed hypnotherapy by a trained behavioral therapist. The treatment protocol developed for the proposed study was adapted from the empirically-supported Manchester Protocol for gut-directed hypnotherapy. At each visit, a voluntary, pleasant, and dream-like state of deep relaxation will be induced and suggestions made for greater relaxation, abdominal comfort, and normalization of gut function. The first session will be 90 minutes in duration and the remaining sessions will be 60 minutes. At the first session, participants will be provided with 30 minutes of education on the nature of the gut-brain axis and hypnotherapy before they undergo hypnotherapy.	Other: Standard Medical Therapy; Standard medical treatment will be administered by board certified gastroenterologists; Behavioral: Gut-directed hypnotherapy; Eight session gut-directed hypnotherapy for IBS symptoms adapted from the evidence-based Manchester protocol for treatment of IBS.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IBS Symptom Severity	The IBS Symptoms Severity Score (IBS-SSS) is a 5-item measure that asks participants to rate abdominal pain intensity, abdominal distension, dissatisfaction with bowel habits, and IBS life interference on a 0-100 scale. The IBS-SSS is a validated measure of IBS symptom severity and a recommended outcome measure for IBS treatment trials	Immediately post-treatment, 3-months post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Upper Gastrointestinal Symptoms	Upper gastrointestinal symptoms will be measured using the Patient Assessment of Upper Gastrointestinal Symptoms (PAGI-SYM), a commonly used 20-item self-report measure of upper gastrointestinal symptoms with good reliability and construct validity.	Immediately post-treatment, 3-months post-treatment
IBS-related Quality of Life	IBS-related Quality of Life will be assessed using The Irritable Bowel Syndrome Quality of Life scale, a 34-item, psychometrically valid self-report measure of IBS-related QOL.	Immediately post-treatment, 3-months post-treatment
Visceral Sensitivity	Visceral sensitivity will be evaluated by the Visceral Sensitivity Index (VSI). a 15-item measure developed to assess gastrointestinal specific anxiety. Visceral sensitivity has been identified as an important contributor to IBS symptom severity and a treatment target for IBS treatment. The VSI has excellent psychometric properties.	Immediately post-treatment, 3-months post-treatment
Emotional Distress	Emotional Distress will be measured using the 8-item anxiety symptom and 8-item depressive symptom self-report measures from the Patient Reported Outcome Measurement Information System (PROMIS), which are extensively validated an have previously been used in IBS research.	Immediately post-treatment, 3-months post-treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weekly Ratings of GI Health and Medication Use	Participants will rate upper abdominal pain, lower abdominal pain, abdominal distension, excess wind, disturbance in bowel movement, nausea, and vomiting on a scale from 0, no symptoms, to 10, severe symptoms. Participants will also rate their well-being over the past week on a scale from 0, no well-being, to 10, the most well-being possible. Participants will also be asked to report their opioid and cannabis use over the past week.	Once a week for 9 weeks hypnotherapy treatment

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Investigators: Principal Investigator: Louis Liu, University Health Network, Toronto

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): December 29, 2024
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: February 8, 2023
• First Submitted That Met QC Criteria: March 15, 2024
• First Posted (Actual): March 22, 2024

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 15, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Disease; Congenital Abnormalities; Hematologic Diseases; Gastrointestinal Diseases; Hemorrhagic Disorders; Genetic Diseases, Inborn; Connective Tissue Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Hemostatic Disorders; Skin Diseases, Genetic; Skin Abnormalities; Collagen Diseases; Syndrome; Irritable Bowel Syndrome; Ehlers-Danlos Syndrome
• Other Study ID Numbers: 22-5277

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No