Gastroenterology · Medical Literature
The WISH 2.0 Intervention for Irritable Bowel Syndrome: Protocol for a Pilot Randomized Controlled Trial.
Abstract
There is a critical need for acceptable, scalable, and mechanistically targeted behavioral health interventions for irritable bowel syndrome (IBS), known as brain-gut behavior therapies (BGBTs). Although positive psychology (PP) interventions, which focus on the cultivation of positive psychological well-being, have been linked to improved health outcomes across diverse medical populations, they have not yet been investigated in IBS. To address this gap, we developed WISH (Well-Being in IBS: Strengths and Happiness), a novel, 9-week, phone-delivered PP-based BGBT for individuals with IBS. This randomized controlled trial (RCT) aims to evaluate the feasibility, acceptability, preliminary effects, and candidate gut-brain mechanisms of a 9-week phone-delivered PP intervention for IBS compared with a time- and attention-matched educational control. The WISH 2.0 trial is a parallel-group, 9-week pilot RCT that aims to enroll 50 adults meeting Rome IV criteria for IBS. Participants are randomized (1:1), stratified by IBS subtype and gender, to either the WISH 2.0 intervention or an educational control condition. Both conditions consist of 9 weekly 30-minute phone sessions accompanied by weekly manualized exercises. Primary outcomes are feasibility (proportion completing ≥6 of 9 sessions) and acceptability (weekly ease and utility ratings). Secondary outcomes include WISH 2.0's preliminary effects on health-related, health behavior, and psychological outcomes, assessed at 4 time points: baseline, intervention midpoint, the postintervention assessment, and the 3-month postintervention assessment. Candidate gut-brain mechanisms that might underlie WISH 2.0's effects, including changes in autonomic function (heart rate variability), interoception (self-report measure), gene expression (whole transcriptome RNA sequencing), and immune system activity (serum inflammatory biomarkers), will be explored before and after the intervention. The trial was approved by the Mass General Brigham Institutional Review Board and prospectively registered at ClinicalTrials.gov in March 2025. Funding was awarded in June 2025. Following a study start-up period, recruitment commenced in October 2025 and is ongoing. As of July 2026, 20 participants have been enrolled. Study completion is anticipated in August 2028. This trial will determine the feasibility and acceptability of WISH 2.0, a novel PP intervention for IBS. Comparative results between WISH 2.0 and an educational control, including the possibility of equivalent outcomes, will provide important mechanistic insights and facilitate further optimization of BGBTs for IBS, informing a future fully powered efficacy trial.
Clinical relevance
Irritable bowel syndrome (IBS) affects a substantial portion of the general population and remains inadequately served by pharmacologic therapies alone, creating a pressing need for scalable, mechanistically targeted brain-gut behavior therapies (BGBTs). This trial addresses a specific evidence gap by being the first to investigate a positive psychology (PP)-based BGBT in IBS, a modality already linked to improved health outcomes across other medical populations. With recruitment actively ongoing as of mid-2026, the WISH 2.0 trial is timely for gastroenterologists and behavioral health specialists seeking to expand the BGBT armamentarium beyond established modalities such as gut-directed hypnotherapy and cognitive behavioral therapy.
Key findings
1. Study design: Parallel-group, 9-week pilot RCT targeting 50 adults meeting Rome IV criteria for IBS, with 1:1 randomization stratified by IBS subtype and gender, comparing WISH 2.0 (a phone-delivered PP-based BGBT) to a time- and attention-matched educational control. 2. Intervention structure: WISH 2.0 consists of 9 weekly 30-minute phone sessions with accompanying manualized exercises, designed to cultivate positive psychological well-being as a candidate therapeutic mechanism in IBS. 3. Primary outcomes: Feasibility is operationalized as the proportion of participants completing ≥6 of 9 sessions; acceptability is measured via weekly ease and utility ratings — both are pre-specified, quantifiable benchmarks appropriate for a pilot trial. 4. Secondary outcomes: Preliminary effects on health-related, health behavior, and psychological outcomes are assessed at 4 time points (baseline, midpoint, post-intervention, and 3-month follow-up), enabling evaluation of both acute and sustained response. 5. Mechanistic endpoints: Candidate gut-brain mechanisms are prospectively explored via heart rate variability (autonomic function), self-report interoception measures, whole transcriptome RNA sequencing (gene expression), and serum inflammatory biomarkers — representing a multimodal biobehavioral mechanistic framework. 6. Enrollment status (as of July 2026): 20 of 50 target participants enrolled since recruitment commenced in October 2025; study completion anticipated August 2028. No efficacy or safety data are available at this protocol stage.
Practice implications
Clinicians managing IBS patients with suboptimal responses to conventional pharmacotherapy or existing BGBTs should be aware of WISH 2.0 as an emerging, phone-delivered PP intervention that may offer a scalable, low-barrier complement to current care, particularly for patients with limited access to in-person behavioral health services. The trial's mechanistic substudies — encompassing HRV, interoception, transcriptomics, and inflammatory biomarkers — will help identify which biological and psychological profiles predict response, potentially enabling future patient-level selection for PP-based BGBTs. Pending feasibility and acceptability results, gastroenterology practices should anticipate that positive findings will support a fully powered efficacy RCT, and eligible patients meeting Rome IV IBS criteria may be considered for referral to the ongoing trial.