Clinical trial NCT06940596: Exclude or Expose in Irritable Bowel Syndrome: What Works for Whom and How?
Official title: Exclude or Expose in Irritable Bowel Syndrome: What Works for Whom, and How? A Randomized Controlled Trial of Internet-Delivered FODMAP Diet Versus Exposure-Based Cognitive Behavioral Therapy
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Irritable Bowel Syndrome (IBS)
Intestinal Diseases
Gastrointestinal Disease
Keywords: Irritable Bowel Syndrome
FODMAP Diet
Behavior Therapy
Gastrointestinal Diseases
Cognitive Behavioral Therapy
Exposure Based Cognitive Behavioral Therapy
Intestinal Diseases
Digestive System Diseases
Low FODMAP Diet
Lead sponsor: University of Melbourne
Sponsor class: OTHER
Collaborators: name: Monash University
First posted: 2025-04-23
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized to one of two treatment arms. The randomization schedule will be generated using http://www.randomization.com. Participants will be stratified by site (Australia or US) before randomization.
Primary purpose: TREATMENT

Brief summary: This research project will assess how two treatments for irritable bowel syndrome (one dietary and one behavioral) work and for whom. This will be done by assessing moderators (what treatment works for who and in what context) and mediators (how treatment works). Investigators will also assess how the diet and behavioral treatments affect IBS symptoms during treatment. Participants will be randomized to either: i. A FODMAP diet online program that focuses on modifying the consumption of foods high or moderate in fermentable carbohydrates (FODMAPS) to manage IBS symptoms. or, ii. An Exposure-based Cognitive Behavioral Therapy (E-CBT) online program for IBS that focuses on changing symptom-related behaviors which are known to worsen IBS symptoms.

Detailed description: This research uses a randomized controlled trial to investigate the treatment of irritable bowel syndrome (IBS). A range of treatments for IBS are available, but each work for only a portion of patients, and it is unclear why. This research project will assess how two treatments (one dietary and one behavioral) work and for whom. Investigators will do this by assessing moderators (what treatment works for who and in what context) and mediators (how treatment works). This project will also assess how the diet and behavioral treatments affect IBS symptoms during treatment. Participants will be randomized to either: i. A FODMAP diet online program that focuses on modifying the consumption of foods high or moderate in fermentable carbohydrates (FODMAPS) to manage IBS symptoms. This treatment involves 3-phases: FODMAP restriction (phase 1), FODMAP re-introduction (phase 2), and FODMAP personalization (phase 3), or, ii. An Exposure-based Cognitive Behavioral Therapy (E-CBT) online program for IBS that focuses on symptom-related behaviors such as avoidance of activities and foods, excessive toilet visits, and behaviors to control symptoms which are known to worsen IBS symptoms. E-CBT uses daily self-observation and exposure exercises to change these behaviors to relieve IBS symptoms. Investigators believe that both treatments, FODMAP diet and E-CBT, will lead to an improvement in IBS gastrointestinal symptoms. Primary moderators and mediators to be assessed include gastrointestinal symptom anxiety, food avoidance behaviour and FODMAP intake.

Eligibility criteria: Inclusion Criteria: Each participant must meet all of the following criteria to be enrolled in this trial:

* Living in Australia or the United States
* Aged 18 years or older
* Body Mass Index (BMI) \[Equation\]18.5kg/m2 and \[Equation\] 34.9kg/m2
* Diagnosed with IBS by a General Practitioner, Family Physician, or Gastroenterologist, or Advanced Specialist Dietitian
* Currently fulfill Rome IV criteria for IBS
* Symptomatic at the time of recruitment (IBS-SSS \> 175)
* Access to a computer and internet
* Sufficient English language and computer skills to complete a text-based online treatment
* Willing to make dietary or behavioral changes in line with the allocated treatment program
* Ability to provide informed consent

Exclusion Criteria:Patients meeting any of the following criteria will be excluded from the trial:

* Presence or known history of other GI disease (e.g. coeliac disease, Inflammatory Bowel Disease) or history of gastrointestinal cancer
* History of major gastrointestinal surgery (not appendectomy, cholecystectomy or hemorrhoidectomy)
* Individuals who report alarm symptoms (e.g., blood in stool, recent unexplained/unintentional weight loss \>5% body weight, a recent change in bowel habits if \>50 years, family history of gastrointestinal cancer or gastrointestinal diseases, large volumes of diarrhea occurring at night, fever associated with gut symptoms, recurrent vomiting, persistent unexplained iron deficiency) will be excluded if appropriate medical investigations have not been conducted, unless written medical approval is provided from a general practitioner, family physical, or gastroenterologist.
* Diagnosis of major disease that could explain current gastrointestinal symptoms such as severe diabetic, cardiac, liver, neurological, neuropathy disease
* History or current diagnosis of psychotic disorder or bipolar disorder
* Current diagnosis of substance abuse disorder or major depressive disorder or active suicidal ideation
* History or current diagnosis of an eating disorder
* Current enteral/parenteral feeding or use of supplemental feeds (e.g. Ensure)
* Pregnant or lactating or planning to become pregnant during the 12-week intervention period
* Commenced or change in dose of antibiotics and medications that potentially affect the gastrointestinal transit (e.g. anti-diarrheals and laxatives) in the 3 months preceding study commencement.
* Commenced taking or changed dose of probiotics, prebiotics, fibre supplements and digestive enzymes in the 3 months preceding study commencement
* Commenced or change dose in psychotropic medication in the 3 months preceding study commencement
* Are currently undertaking behavioral therapy for IBS (including cognitive behavioral therapy, CBT), or have undertaken clinician-delivered behavioral therapy for the treatment of IBS
* Are currently undertaking or have undertaken a dietitian-prescribed and delivered restrictive diet for IBS (e.g., FODMAP diet).

Primary outcomes:
measure: Gastrointestinal Symptom Rating Scale-Irritable Bowel Syndrome (GSRS-IBS )
timeFrame: Measured weekly between baseline (prior to intervention) and after intervention completed (week 12).
Secondary outcomes:
measure: Change from baseline in Gastrointestinal Symptom Rating Scale-Irritable Bowel Syndrome (GSRS-IBS)
timeFrame: Baseline and 3-and 6 month follow up time points after intervention completed (week 12).
measure: Change from baseline in Irritable Bowel Syndrome - Symptom Severity Score (IBS-SSS) questionnaire
timeFrame: Baseline, after intervention completed (week 12), and at follow up time points of 3-and 6 months following the 12-week intervention.
measure: Change from baseline in IBS quality of life (IBS-QOL) questionnaire
timeFrame: Baseline, after intervention completed (week 12), and at follow up time points of 3-and 6 months following the 12-week intervention.
measure: Change from baseline in Nine Item ARFID (Avoidant Restrictive Food Intake Disorder) Screen (NIAS) questionnaire
timeFrame: Baseline, after intervention completed (week 12), and at follow up time points of 3-and 6 months following the 12-week intervention.
measure: Change from baseline in Fear of Food Questionnaire (FFQ) questionnaire
timeFrame: Baseline, after intervention completed (week 12), and at follow up time points of 3-and 6 months following the 12-week intervention.
measure: Change from baseline in Patient Health Questionnaire-12 (PHQ-12) (derived from PHQ-15) questionnaire
timeFrame: Baseline, after intervention completed (week 12), and at follow up time points of 3-and 6 months following the 12-week intervention.
measure: Change from baseline in Generalized anxiety disorder (GAD-7) questionnaire
timeFrame: Baseline, after intervention completed (week 12), and at follow up time points of 3-and 6 months following the 12-week intervention.
measure: Change from baseline in Patient Health Questionnaire (PHQ-9) questionnaire
timeFrame: Baseline, after intervention completed (week 12), and at follow up time points of 3-and 6 months following the 12-week intervention.
measure: Change from baseline in Gastrointestinal Specific Anxiety (GSA) measured using Visceral Sensitivity Index (VSI)
timeFrame: Baseline, after intervention completed (week 12), and at follow up time points of 3-and 6 months following the 12-week intervention.
measure: Change from baseline in Avoidance behavior measured using Irritable Bowel Syndrome-Behavioural Responses Questionnaire (IBS-BRQ)
timeFrame: Baseline, after intervention completed (week 12), and at follow up time points of 3-and 6 months following the 12-week intervention.
measure: Change from baseline in Total FODMAP intake measured using 3-day food diary
timeFrame: Baseline, after intervention completed (week 12), and at follow up time points of 3-and 6 months following the 12-week intervention.
measure: Change from baseline in stool frequency and consistency using 7-day stool diary based on Bristol Stool Form Scale (BSFS)
timeFrame: Baseline, after intervention completed (week 12), and at follow up time points of 3-and 6 months following the 12-week intervention.
measure: Gastrointestinal microbiome composition and function using stool sample using OMNIgene GUT
timeFrame: Gastrointestinal microbiome composition and function will be measured 2nd weekly between baseline (prior to intervention) and after intervention completed (week 12) as exploratory mediators.
measure: Individual FODMAPs' intake using 3-day food diary
timeFrame: Will be measured 2nd weekly between baseline (prior to intervention) and after intervention completed (week 12) as exploratory mediators.
measure: Gastrointestinal Symptom Rating Scale-Irritable Bowel Syndrome GSRS-IBS
timeFrame: Baseline (prior to start of intervention) as an exploratory moderator.
measure: IBS quality of life (IBS-QOL) questionnaire
timeFrame: Baseline (prior to start of intervention) as an exploratory moderator.
measure: Fear of Food Questionnaire (FFQ) questionnaire
timeFrame: Baseline (prior to start of intervention) as an exploratory moderator.
measure: Nine Item ARFID (Avoidant Restrictive Food Intake Disorder) Screen (NIAS) questionnaire
timeFrame: Baseline (prior to start of intervention) as an exploratory moderator.
measure: Patient Health Questionnaire-12 (PHQ-12) (derived from PHQ-15) questionnaire
timeFrame: Baseline (prior to start of intervention) as an exploratory moderator.
measure: Patient Health Questionnaire (PHQ-9) questionnaire
timeFrame: Baseline (prior to start of intervention) as an exploratory moderator.
measure: Generalized anxiety disorder (GAD-7) questionnaire
timeFrame: Baseline (prior to start of intervention) as an exploratory moderator.
measure: Gastrointestinal microbiome composition and function using stool sample using a stool sample collection kit.
timeFrame: Baseline (prior to start of intervention) as an exploratory moderator.
measure: IBS subtype using 7-day stool diary based on Bristol Stool Form Scale (BSFS).
timeFrame: Baseline (prior to start of intervention) as an exploratory moderator.
measure: Client Satisfaction Questionnaire
timeFrame: End of the 12-week intervention and at 3-and 6 months follow up time points after 12-week intervention..
measure: Proportion of participants who achieve a change from baseline in Gastrointestinal Symptom Rating Scale-Irritable Bowel Syndrome (GSRS-IBS) of >30% total score
timeFrame: Baseline and after intervention completed (week 12)
measure: Proportion of participants who achieve a change from baseline in Irritable Bowel Syndrome - Symptom Severity Score (IBS-SSS) of ≥50 points total score.
timeFrame: Baseline and after intervention completed (week 12)
Other outcomes:
measure: Gastrointestinal Specific Anxiety (GSA) measured using Visceral Sensitivity Index (VSI)
timeFrame: VSI will be measured 2nd weekly between baseline (prior to intervention), after intervention (week 12) and and at follow up timepoints of 3-and 6 months following the 12-week intervention as a putative mediator.
measure: Avoidance behavior measured using Irritable Bowel Syndrome-Behavioural Responses Questionnaire (IBS-BRQ)
timeFrame: IBS-BRQ will be measured 2nd weekly between baseline (prior to intervention), after intervention (week 12) and and at follow up timepoints of 3-and 6 months following the 12-week intervention as a putative mediator.
measure: Total FODMAP intake measured using 3-day food diary
timeFrame: Total FODMAP intake will be measured 2nd weekly between baseline (prior to intervention), after intervention (week 12) and and at follow up timepoints of 3-and 6 months following the 12-week intervention as a putative mediator.
measure: Treatment preference
timeFrame: Baseline (prior to start of intervention) as a putative moderator.
measure: Gastrointestinal Specific Anxiety (GSA) measured using Visceral Sensitivity Index (VSI)
timeFrame: Baseline (prior to start of intervention) as a putative moderator.
measure: Avoidance behavior measured using Irritable Bowel Syndrome-Behavioural Responses Questionnaire (IBS-BRQ)
timeFrame: Baseline (prior to start of intervention) as a putative moderator.
measure: Total FODMAP intake measured using 3-day food diary
timeFrame: Baseline (prior to start of intervention) as a putative moderator.
measure: Credibility expectancy questionnaire (CEQ) questionnaire
timeFrame: End of week 2 of 12-week intervention
measure: Working alliance inventory for guided internet intervention (WAI-I) questionnaire
timeFrame: End of week 2 of 12-week intervention
Locations:
Study officials:
affiliation: University of Melbourne
name: Associate Professor Jessica Biesiekierski
role: PRINCIPAL_INVESTIGATOR
References:
citation: Biesiekierski JR, Manning LP, Murray HB, Vlaeyen JWS, Ljotsson B, Van Oudenhove L. Review article: exclude or expose? The paradox of conceptually opposite treatments for irritable bowel syndrome. Aliment Pharmacol Ther. 2022 Aug;56(4):592-605. doi: 10.1111/apt.17111. Epub 2022 Jul 1.