Clinical trials landscape¶
TL;DR — ClinicalTrials.gov held 1,171 registered studies for irritable bowel syndrome on 2026-09-02: 696 completed, 111 recruiting, 57 not yet recruiting, 17 active but not recruiting, 63 terminated, 24 withdrawn, 185 of unknown status. Only 105 are phase 3 and 80 phase 4; 592 carry no phase designation at all (behavioural, dietary, device and observational studies). Condition-plus-intervention API searches returned 133 probiotic, 97 FODMAP, 50 cognitive behavioural therapy, 37 faecal microbiota transplantation, 26 rifaximin and 27 linaclotide records — i.e. the pipeline is dominated by non-drug and microbiome interventions, not by novel pharmacology. Only 21 phase 3 studies have started since 1 January 2021, and several of those are traditional Chinese medicine trials or paediatric extensions of approved drugs. Large industry phase 2 programmes include camlipixant, a P2X3 antagonist, in IBS-D and IBS-M (NCT07519395, GlaxoSmithKline, n=420), and brenipatide, an investigational subcutaneous drug being tested separately in IBS-D (NCT07545759, n=531) and IBS-C (NCT07545772, n=342) by Eli Lilly. The largest completed trials that changed practice in this era were investigator-led and non-commercial: ATLANTIS (amitriptyline in primary care), CARIBS (diet vs drugs), DOMINO (a smartphone FODMAP app beating an antispasmodic in primary care, 71% vs 61% responders, p=0.03; Carbone 2022, PMID 35483886), and ACTIB (remote CBT). All counts and records in this page were retrieved live from the ClinicalTrials.gov v2 API on 2026-09-02.
The registry at a glance (2026-09-02)¶
| Slice | Count |
|---|---|
| All registered IBS studies | 1,171 |
| Completed | 696 |
| Recruiting | 111 |
| Not yet recruiting | 57 |
| Active, not recruiting | 17 |
| Terminated | 63 |
| Withdrawn | 24 |
| Unknown status | 185 |
| Phase 1 | 43 |
| Phase 2 | 177 |
| Phase 3 | 105 |
| Phase 4 | 80 |
| No phase assigned | 592 |
| Intervention term | Studies |
|---|---|
| Probiotic | 133 |
| FODMAP | 97 |
| Cognitive behavioural therapy | 50 |
| Faecal microbiota transplantation | 37 |
| Rifaximin | 26 |
| Linaclotide | 27 |
| Hypnotherapy | 22 |
| Acupuncture | 18 |
| Vagus nerve stimulation | 10 |
| Tenapanor | 9 |
| Amitriptyline | 4 |
| Ebastine | 4 |
The shape of that table is the finding. Four amitriptyline studies exist in the registry for a drug that the largest IBS trial ever run showed to be effective in primary care (gut-brain-neuromodulators); 146 probiotic studies exist for a class whose GRADE certainty is low to very low across almost every analysis (microbiome).
Novel mechanisms in industry development¶
| NCT | Agent / mechanism | Phase | n | Status | Sponsor | Start |
|---|---|---|---|---|---|---|
| NCT07519395 | Camlipixant (P2X3 receptor antagonist) vs placebo, abdominal symptoms in IBS-D and IBS-M | 2 | 420 | Recruiting | GlaxoSmithKline | 2026-04-08 |
| NCT07545759 | Brenipatide (LY3537031) vs placebo, subcutaneous, IBS-D | 2 | 531 | Recruiting | Eli Lilly | 2026-05-06 |
| NCT07545772 | Brenipatide (LY3537031) vs placebo, subcutaneous, IBS-C | 2 | 342 | Recruiting | Eli Lilly | 2026-04-29 |
| NCT06206265 | Psilocybin plus psychotherapy, open-label delayed-treatment design | 2 | 14 | Active, not recruiting | TRYP Therapeutics | 2024-01-17 |
| NCT06727422 | Rifaximin + N-acetylcysteine (two dose combinations) vs placebo in IBS-D | 2 | 225 | Recruiting | Mark Pimentel, MD | 2026-02-04 |
| NCT06247046 | Live SK08 powder (live biotherapeutic) vs placebo in IBS-D | 3 | 1,298 | Recruiting | Guangzhou Zhiyi Biotechnology | 2024-03-16 |
| NCT07168434 | Saccharomyces boulardii CNCM I-745 vs placebo | 3 | 406 | Recruiting | Biocodex | 2025-10-22 |
| NCT05815602 | Ebastine vs mebeverine (H1-antagonist vs antispasmodic) | 3 | 200 | Recruiting | Guy Boeckxstaens | 2023-03-30 |
| NCT07114055 | Ebastine vs placebo in IBS-D | 3 | 60 | Recruiting | Md. Hazrat Ali | 2025-08-15 |
| NCT06221111 | Rimegepant (CGRP antagonist) vs placebo for IBS pain | 2 | 39 | Completed | Mayo Clinic | 2024-06-06 |
| NCT07522255 | Rifaximin in bloating-predominant functional bowel disorders | 3 | 78 | Not yet recruiting | Mahidol University | 2026-04 |
P2X3 antagonism is an afferent-nerve mechanism consistent with the visceral-hypersensitivity model (brain-gut-axis-and-visceral-hypersensitivity). The registry does not state brenipatide's molecular target, so no mechanism is inferred here. The ebastine programme is the therapeutic test of the mast-cell/histamine hypothesis and now includes an active-comparator phase 3 against mebeverine (NCT05815602) — worth watching given that mebeverine itself has a null pooled estimate (antispasmodics-and-peppermint).
Paediatric label extensions of approved drugs¶
| NCT | Drug | Phase | n | Status | Sponsor |
|---|---|---|---|---|---|
| NCT04880876 | Eluxadoline 25/100 mg in paediatric IBS-D | 3 | 124 | Enrolling by invitation | AbbVie |
| NCT05643534 | Tenapanor in IBS-C, ages 12 to <18 | 3 | 180 | Active, not recruiting | Ardelyx |
| NCT05905926 | Tenapanor safety, ages 6 to <18, IBS-C | 3 | 150 | Enrolling by invitation | Ardelyx |
| NCT06553547 | Tenapanor dose-ranging, ages 6 to <12, IBS-C | 2 | 72 | Completed | Ardelyx |
| NCT06639984 | Psyllium in paediatric IBS | 2 | 110 | Recruiting | Bruno Chumpitazi, MD |
This knowledge base is adult-scoped; these are listed because they represent a substantial share of current commercial phase 3 activity in IBS.
Microbiome interventions¶
| NCT | Study | Phase | n | Status | Sponsor |
|---|---|---|---|---|---|
| NCT04691544 | Donor vs autologous FMT for IBS | 3 | 450 | Active, not recruiting | University Hospital of North Norway |
| NCT06433180 | FMT capsules vs sham in severe IBS | 3 | 150 | Not yet recruiting | AP-HP, Paris |
| NCT04014413 | Multicondition FMT safety/efficacy platform; 450 total enrollment, IBS subgroup size not stated | NA | 450 total | Recruiting | Chinese University of Hong Kong |
| NCT05803980 | FMT for non-constipated IBS | NA | 35 | Recruiting | Policlinico Gemelli, Rome |
| NCT06948461 | Freeze-dried oral FMT in IBS-D or recurrent C. difficile | 2 | 63 | Not yet recruiting | PharmaPlanter Technologies |
| NCT05633706 | SIMBA fluid-biopsy capsule for small-intestinal dysbiosis; 300 total across seven conditions and healthy controls | NA | 300 total | Recruiting | Nimble Science |
| NCT07517029 | Gut microbiome in post-infectious IBS | Obs. | 315 | Recruiting | Policlinico Gemelli, Rome |
| NCT06801184 | Intestinal microbiota in IBS-C with methane production | Obs. | 40 | Recruiting | Hospices Civils de Lyon |
The Norwegian donor-vs-autologous phase 3 (NCT04691544, n=450) is the study most likely to resolve the FMT contradiction described on microbiome, because it is powered and uses the design that separates donor effect from procedure effect.
Diet and behavioural interventions¶
| NCT | Study | n | Status | Sponsor |
|---|---|---|---|---|
| NCT04270487 | DOMINO: smartphone FODMAP-lowering diet app vs otilonium bromide in primary care | 472 | Completed (phase 4) | KU Leuven |
| NCT03687814 | Low FODMAP + PEG 3350 vs sham diet + PEG 3350 in IBS-C | 78 | Recruiting | University of Michigan |
| NCT05120752 | Low FODMAP in the absence of lactose malabsorption | 60 | Recruiting | UZ Brussel |
| NCT04974593 | Predictive value of lactose breath testing for lactose-free-diet response | 90 | Recruiting | UZ Brussel |
| NCT06912828 | GWAS for genetic predictors of dietary-intervention success (Med-LFD) | 100 | Recruiting | Attikon Hospital |
| NCT05721742 | Virtual dietitian consults within an electronic IBS pathway | 76 | Recruiting | Nova Scotia Health Authority |
| NCT04133519 | Regulora digital gut-directed hypnotherapy vs digital muscle relaxation | 378 | Completed | metaMe Health |
| NCT03899779 | Face-to-face vs online hypnotherapy vs online psychoeducation | 282 | Completed | Maastricht UMC |
| NCT06297785 | Online gut-directed hypnotherapy | 50 | Completed | Sahlgrenska |
| NCT06866106 | WISH 2.0: positive psychology vs educational intervention | 50 | Recruiting | Massachusetts General Hospital |
| NCT01529567 | CBT with vs without exposure therapy | 311 | Completed | Karolinska Institutet |
| NCT00934973 | MIBS: mebeverine, methylcellulose, placebo, CBT website | 135 | Completed (phase 4) | Hazel Everitt |
| (ACTIB and ATLANTIS) | Registered on the ISRCTN registry (ISRCTN44427879 and ISRCTN48075063), not on ClinicalTrials.gov — see psychological-therapy and gut-brain-neuromodulators | — | — | — |
DOMINO deserves its result stated: 459 primary-care IBS patients randomised to 8 weeks of otilonium bromide 40 mg three times daily or a smartphone FODMAP-lowering diet app, followed for 24 weeks. Responder rate (IBS-SSS improvement ≥50) at 8 weeks was 71% (155/218) with diet versus 61% (133/217) with otilonium (p=0.03), and 77% vs 62% (p=0.004) in the Rome IV-positive subgroup. Adherence was 94% with diet versus 73% with the drug (p<0.001). The advantage was already present at 4 weeks (62% vs 51%, p=0.02). Predictors of response were female sex for diet (OR 2.08, p=0.04) and PHQ15 for otilonium (OR 1.10, p=0.02). The authors' conclusion: "A FODMAP-lowering diet should be considered the first-line treatment for IBS in primary care" (Carbone 2022, PMID 35483886). Post-hoc analyses have examined subtype effects (Di Rosa 2024, PMID 39086991), inflammatory biomarkers (Tack 2025, PMID 41436948) and eosinophil-driven immune activation (Routhiaux 2026, PMID 41670574).
Neuromodulation devices¶
| NCT / publication | Intervention | n | Status |
|---|---|---|---|
| NCT06090110 | Vagal nerve stimulation vs sham | 166 | Recruiting (Maastricht UMC) |
| NCT05519683 | Home transcutaneous electrical acustimulation vs escitalopram | 160 | Recruiting (University of Michigan), phase 2/3 |
| NCT07425145 | Transcutaneous electrical acustimulation for IBS-D, multicentre | 200 | Not yet recruiting |
| Liu 2024, PMID 39689011 | Transcutaneous auricular vagus nerve stimulation in IBS-C, single-centre single-blind RCT | — | Published |
| Veldman 2025, PMID 39867596 | Systematic review of vagus nerve stimulation across GI disorders | — | Published |
| NCT07798180 | Transauricular neurostimulation for abdominal pain in DGBI (paediatric) | 30 | Recruiting |
Vagal and acustimulation approaches are the fastest-growing device category, at 11 registered studies. The Michigan trial comparing home acustimulation directly against escitalopram (NCT05519683) is unusual in using an active drug comparator.
What the landscape is missing¶
- Head-to-head licensed-drug comparisons. The 1,171-record registry snapshot contained no trial comparing two drugs both licensed specifically for IBS; the active ebastine-versus-mebeverine trial is a comparison of an investigational repurposing candidate with an antispasmodic (NCT05815602). Licensed-drug rankings therefore remain indirect (constipation-predominant-pharmacotherapy, diarrhoea-predominant-pharmacotherapy).
- Neuromodulator versus behavioural therapy in primary care. Targeted PubMed and ClinicalTrials.gov searches on 2026-09-02 retrieved no amitriptyline-versus-CBT trial (OPEN-QUESTIONS.md).
- Criteria-stratified trials. The registry snapshot and a targeted PubMed search on 2026-09-02 retrieved no study stratifying treatment response by Rome III/IV/V status (diagnosis-and-rome-criteria).
- Prevention of post-infectious IBS. A validated risk score exists (Thabane 2009, PMID 19568228); targeted PubMed and registry searches on 2026-09-02 retrieved no prevention trial using it (post-infectious-ibs).
- Open-label placebo as an intervention arm in a pragmatic trial. A targeted PubMed and registry search on 2026-09-02 retrieved no such pragmatic trial, despite three explanatory randomised studies (placebo-response-and-trial-design).
- Long-term controlled follow-up. Most drug trials stop at 12–26 weeks in a lifelong relapsing condition; uncontrolled 52-week safety or observational extensions exist for some agents.
- Work and social function as primary endpoints. Targeted PubMed and registry searches on 2026-09-02 found work-productivity analyses as secondary/economic outcomes, but no IBS treatment trial with work or social function as the primary endpoint, despite 81.8% overall work impairment (quality-of-life-and-stigma).
Registry hygiene notes¶
- 185 of 1,171 studies (15.8%) carry "unknown" status, meaning the record has passed its expected completion date without an update. Any statement about "what is currently being tested" based on registry status alone will overcount active work.
- 63 terminated and 24 withdrawn studies are recorded; reasons are not systematically comparable.
- Two of the most influential recent trials in this knowledge base — ATLANTIS and ACTIB — are registered on the ISRCTN registry (ISRCTN48075063 and ISRCTN44427879), not on ClinicalTrials.gov, so a ClinicalTrials.gov-only survey systematically under-represents UK publicly funded trials.
Open questions¶
- Will camlipixant (NCT07519395) validate P2X3 antagonism as an IBS mechanism, and if it fails, what does that say about the visceral-hypersensitivity model?
- Will the Norwegian donor-vs-autologous FMT phase 3 (NCT04691544, n=450) resolve the FMT contradiction?
- Does ebastine beat placebo — and mebeverine — in adequately powered trials (NCT05815602, NCT07114055)?
- Why are there 146 probiotic studies and 4 amitriptyline studies for a condition where the tricyclic evidence is stronger?
- Will any trial adopt Rome V, and will that change measured effect sizes (Staller 2026, PMID 42392123)?
- Should DOMINO's conclusion — diet first-line in primary care (Carbone 2022, PMID 35483886) — be tested against ATLANTIS's amitriptyline in the same setting?
Related pages¶
- dietary-therapy — CARIBS and DOMINO in full.
- gut-brain-neuromodulators — ATLANTIS.
- psychological-therapy — ACTIB and the digital hypnotherapy trials.
- microbiome — the FMT contradiction the Norwegian trial may resolve.
- brain-gut-axis-and-visceral-hypersensitivity — the mechanisms camlipixant and ebastine test.
- placebo-response-and-trial-design — why endpoint choice drives these trials' apparent success.
- guidelines — what current guidance rests on.
References¶
- Carbone F, et al. Diet or medication in primary care patients with IBS: the DOMINO study - a randomised trial supported by the Belgian Health Care Knowledge Centre (KCE Trials Programme) and the Rome Foundation Research Institute. Gut. 2022;71(11):2226-2232. PMID 35483886 (NCT04270487)
- Di Rosa C, et al. DOMINO trial post hoc analysis: evaluation of the diet effects on symptoms in IBS subtypes. Therap Adv Gastroenterol. 2024;17:17562848241255296. PMID 39086991
- Tack C, et al. A study on the utility of inflammatory biomarkers in primary care irritable bowel syndrome: a sub analysis of the DOMINO randomized trial. BMC Gastroenterol. 2025;26:69. PMID 41436948
- Routhiaux K, et al. Involvement of Eosinophil-Driven Intestinal Immune Activation in Different Irritable Bowel Syndrome Subtypes and in the Response to a FODMAP Lowering Diet: A Post Hoc Analysis of the Randomized Controlled DOMINO Trial. Gastroenterology. 2026;170(4):818-820. PMID 41670574
- Liu J, et al. Efficacy and Safety of Transcutaneous Auricular Vagus Nerve Stimulation in Patients With Constipation-Predominant Irritable Bowel Syndrome. Am J Gastroenterol. 2024;120(9):2139-2153. PMID 39689011
- Veldman F, et al. Efficacy of vagus nerve stimulation in gastrointestinal disorders: a systematic review. Gastroenterol Rep (Oxf). 2025;13:goaf009. PMID 39867596
- Berry SK, Berry R, Recker D, Botbyl J, Pun L, Chey WD. A Randomized Parallel-group Study of Digital Gut-directed Hypnotherapy vs Muscle Relaxation for Irritable Bowel Syndrome. Clin Gastroenterol Hepatol. 2023;21(12):3152-3159.e2. PMID 37391055 (NCT04133519)
- Ford AC, et al. Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment in primary care (ATLANTIS). Lancet. 2023;402(10414):1773-1785. PMID 37858323 (ISRCTN48075063)
- Everitt HA, et al. Assessing telephone-delivered cognitive-behavioural therapy (CBT) and web-delivered CBT versus treatment as usual in irritable bowel syndrome (ACTIB). Gut. 2019;68(9):1613-1623. PMID 30971419 (ISRCTN44427879)
- Nybacka S, et al. A low FODMAP diet plus traditional dietary advice versus a low-carbohydrate diet versus pharmacological treatment in irritable bowel syndrome (CARIBS). Lancet Gastroenterol Hepatol. 2024;9(6):507-520. PMID 38643782 (NCT02970591)
- Thabane M, Simunovic M, Akhtar-Danesh N, Marshall JK. Development and validation of a risk score for post-infectious irritable bowel syndrome. Am J Gastroenterol. 2009;104(9):2267-74. PMID 19568228
- Staller K, et al. The Rome V criteria for the diagnosis of irritable bowel syndrome in secondary care: a diagnostic accuracy study. Lancet Gastroenterol Hepatol. 2026;11(9):812-820. PMID 42392123
Trial registrations cited above (retrieved live from the ClinicalTrials.gov v2 API, 2026-09-02): NCT07519395, NCT07545759, NCT07545772, NCT06206265, NCT06727422, NCT06247046, NCT07168434, NCT05815602, NCT07114055, NCT06221111, NCT07522255, NCT04880876, NCT05643534, NCT05905926, NCT06553547, NCT06639984, NCT04691544, NCT06433180, NCT04014413, NCT05803980, NCT06948461, NCT05633706, NCT07517029, NCT06801184, NCT04270487, NCT03687814, NCT05120752, NCT04974593, NCT06912828, NCT05721742, NCT04133519, NCT03899779, NCT06297785, NCT06866106, NCT01529567, NCT00934973, NCT06090110, NCT05519683, NCT07425145, NCT07798180, NCT02970591.