Saccharomyces boulardii probiotic for non-constipated IBS (diarrhea or mixed)

A Double-blind, Randomized, Placebo-controlled, Multicenter Trial Evaluating the Efficacy and Safety of Saccharomyces Boulardii CNCM I-745 in Adult Patients With Non-constipated Irritable Bowel Syndrome

This trial will test whether the probiotic Saccharomyces boulardii CNCM I-745 reduces overall symptoms in adults (18–65) with non-constipated IBS compared with placebo after 8 weeks.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 406 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Biocodex (industry)
• Locations: 10 sites (Braga and 9 other locations)
• Trial ID: NCT07168434 on ClinicalTrials.gov

What this trial studies

This is a double-blind, randomized, placebo-controlled Phase 3 multicenter trial comparing Saccharomyces boulardii CNCM I-745 250 mg to matching placebo over a 3-month treatment period. The primary outcome is change in overall IBS symptom severity measured by the IBS-SSS at 8 weeks, with secondary outcomes including quality of life, individual symptom trajectories, and responder rates by EMA criteria. The trial enrolls adults 18–65 with IBS-D or mixed IBS (IBS-SSS ≥175) and excludes constipation-predominant IBS and certain other gastrointestinal conditions. Sites include hospitals in Braga, Lisbon, and Barcelona and the protocol requires participants to maintain usual diet and attend scheduled clinic visits.

Who should consider this trial

Good fit: Adults aged 18–65 with IBS-D or mixed IBS per Rome IV and an IBS-SSS score of at least 175 who can follow study visits and contraceptive guidance if applicable.

Not a fit: Patients with constipation-predominant IBS, recent other significant GI disease, or averaging more than five bowel movements per day during screening are excluded and are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, the probiotic could lower IBS symptom severity and improve quality of life for adults with non-constipated IBS.

How similar studies have performed: Some smaller trials and meta-analyses of various probiotics show modest benefits for IBS symptoms, but evidence specifically for Saccharomyces boulardii in IBS is limited and mixed, so this phase 3 trial aims to provide more definitive data.

Eligibility criteria

Inclusion Criteria:

1. Male or female aged ≥ 18 and ≤ 65 years.
2. Diagnosis of IBS of any subtype, except constipation predominant (IBS-C), according to Rome IV criteria.
3. IBS-SSS total score ≥ 175 at inclusion.
4. Able and willing to maintain their nutrition habits throughout the study participation.
5. Able to understand and willing to comply with study requirements and to provide written informed consent.
6. For women of childbearing potential: willing to use one or more acceptable birth control method throughout the study participation.

Exclusion Criteria:

1. Diagnosis of IBS-C according to Rome IV criteria.
2. Patient with more than 5 bowel movements per day on average during the screening period, according to the patient's diary (BSFS).
3. Severe illness(es) or medical condition(s), including gastrointestinal pathologies (other than IBS): gastrointestinal ulcers, coeliac disease, inflammatory bowel disease, bowel cancer, acute or chronic diarrhea secondary to confirmed infectious gastroenteritis, or enteral or parenteral nutrition.
4. History of abdominal surgery (except for appendectomy, cholecystectomy, surgery for hemorrhoids or cesarian section, more than 6 months prior to inclusion).
5. Familial colorectal cancer syndrome (Lynch, Familial Adenomatous Polyposis).
6. Fecal transplant within 6 months prior to screening.
7. Use of products marketed as prebiotics, probiotics or synbiotics within 2 weeks prior to screening. These products, with the exception of the investigational product, will not be allowed during the trial. Regular cheese or yogurt containing lactic acid bacteria are not an exclusion criterion.
8. Systemic antibiotic or antimycotic treatment within 2 weeks prior to randomization. These treatments are not allowed during the study.
9. Laxatives, antibloating agents, antidiarrheal medication, antispasmodics, within 2 weeks prior to screening. These treatments are not allowed during the study, except loperamide which can be used as rescue medication.
10. Daily or regular non-steroidal anti-inflammatory drugs (NSAIDS) at doses above cardiovascular prophylaxis (low dose aspirin) are not allowed within 2 weeks prior to screening and throughout the study participation.
11. Use of opioids or narcotic analgesics, including tramadol and codeine, within 6 weeks prior to screening. These treatments are not allowed during the study.
12. Treatment with two or more antidepressant/anxiolytic/antipsychotic within 3 months prior to study entry or during the trial. Treatment with a single antidepressant or anxiolytic or antipsychotic agent before and during the trial is allowed provided that the dose is stable within 3 months prior to study entry and during the trial participation.
13. Treatment with anticholinergics for overactive bladder such as solifenacin, darifenacin, oxybutynin, tolterodine, fesoterodin, propiverin, trospium chloride, or mirabegron, within 1 week prior to screening. These treatments are not allowed during the study.
14. Allergy to yeast, especially Saccharomyces boulardii, or known hypersensitivity to one of the components.
15. Patients having a central venous catheter, critically ill patients, and immunocompromised patients.
16. Patients with rare hereditary problems of galactose or fructose intolerance, total lactase deficiency, glucose-galactose malabsorption or sucrase-isomaltase insufficiency.
17. Excessive alcohol consumption (\>7 units/week) and/or drug abuse.
18. Other medical conditions or comorbidities, treatment, which in the opinion of the investigator, would interfere with study compliance or data interpretation.
19. Presenting any significant biological or clinical anomalies that are not compatible with participation in the study according to the investigator.
20. Participant at risk of pregnancy, pregnant or breastfeeding female.
21. Participant under guardianship or curatorship.
22. Participant under the protection of the Court or deprived of liberty.
23. Participant participating in another interventional clinical trial which could interfere with the trial's results or impact the other trial's results; or within 5 half-lives of the study investigational treatment, whichever is longer.
24. Participant whose current state of health does not allow him/her to give consent.

Where this trial is running

Braga and 9 other locations

• Hospital de Braga — Braga, Portugal (RECRUITING)
• Hospital da Luz — Lisbon, Portugal (NOT_YET_RECRUITING)
• Hospital Universitario Vall d'Hebron — Barcelona, Spain (NOT_YET_RECRUITING)
• Hospital Universitario de León — León, Spain (RECRUITING)
• Hospital Universitario Gregorio Marañon & Centro de Salud Pavones — Madrid, Spain (RECRUITING)
• Hospital Clínico San Carlos — Madrid, Spain (NOT_YET_RECRUITING)
• Hospital Universitario La Paz & Hospital Carlos III — Madrid, Spain (NOT_YET_RECRUITING)
• Hospital Universitario Costa del Sol — Marbella, Spain (NOT_YET_RECRUITING)
• Hospital Universitario Regional de Málaga — Málaga, Spain (NOT_YET_RECRUITING)
• Hospital Universitario Central de Asturias & Centro de Salud la Lila — Oviedo, Spain (NOT_YET_RECRUITING)

Study contacts

• Study coordinator: Elise Miclot

Conditions: IBS, IBS-D, IBS, Mixed Symptoms, Irritable Bowel Syndrome, Saccharomyces boulardii, Non-constipated IBS