Efficacy of a mechanism-based psychological intervention for persistent gastrointestinal symptoms in ulcerative colitis and irritable bowel syndrome: results of a three-arm randomised controlled trial (SOMA.GUT-RCT).

Background: Irritable Bowel Syndrome (IBS) and Ulcerative Colitis (UC) are chronic gastrointestinal conditions with differing pathologies but overlapping symptoms and shared risk factors contributing to symptom persistence. Illness-related anxiety and dysfunctional symptom expectations constitute two empirically proven mechanisms of symptom persistence. Yet, the efficacy of a targeted psychological intervention focussing on these mechanisms remains untested. The SOMA.GUT trial tested whether such a mechanism-based intervention can reduce gastrointestinal symptom severity in individuals with IBS or UC. Methods: The SOMA.GUT trial was an investigator-initiated, three-arm randomised controlled trial with nationwide recruitment in Germany of adult patients with either IBS or UC and at least moderate gastrointestinal symptom severity (Irritable Bowel Syndrome-Severity Scoring System, IBS-SSS ≥175). Patients were randomly assigned (1:1:1) to one of three groups: to standard care (SC) alone; to a targeted psychological intervention addressing illness-related anxiety and dysfunctional symptom expectations (GUT.EXPECT + SC); or to a supportive intervention designed to give insights into non-specific treatment effects (GUT.SUPPORT + SC). Randomisation was stratified by gender and diagnosis. Both intervention arms comprised four therapist-guided online sessions. The primary outcome was change in IBS-SSS gastrointestinal symptom severity between baseline and three months in the intention-to-treat population. Key secondary outcomes, measured at six weeks, three, six, and 12 months, included the mechanisms targeted by the GUT.EXPECT intervention. This trial was registered (ISRCTN30800023) and has been completed. Findings: Between April 2022, and February 2024, 2099 patients were screened online for eligibility. Of the 240 patients included in the full analysis set (UC: 126, IBS: 114), 176 (73.3%) self-identified as female, 62 (25.8%) as male and two (0.8%) as diverse. Change in IBS-SSS gastrointestinal symptom severity at three months did not differ significantly between groups (global p = 0.83); SC: -50.4 (95% CI -70.7 to -30.1), GUT.SUPPORT + SC: -55.4 (-75.0 to -35.9) and GUT.EXPECT + SC: -59.4 (-79.4 to -39.4). However, in exploratory analyses, the GUT.EXPECT intervention group showed relevant improvements in illness-related anxiety and expectations about symptom coping at three months compared to SC only, as well as in IBS-SSS gastrointestinal symptom severity at 12 months. No differential treatment effects were observed for UC and IBS, and no intervention-related serious adverse events were reported in any group. Interpretation: While gastrointestinal symptom severity remained similar between the groups at three months, the targeted psychological variables improved, and the symptom improvement observed at 12 months might indicate a delayed effect of the mechanism-based intervention. These findings may support the relevance of the proposed biopsychosocial mechanisms and the potential of psychological interventions in gastrointestinal disorders. However, higher treatment intensity, and broader biopsychosocial targeting may be required to achieve more immediate and clinically meaningful symptom relief. Funding: German Research Foundation (Deutsche Forschungsgemeinschaft, DFG, Project ID: 445297796).