Rifaximin plus N-acetylcysteine (NAC) for diarrhea-predominant IBS

A Phase 2b, Randomized, Double-Blind, Placebo- Controlled, Multicenter Study to Assess the Safety, Efficacy and Pharmacokinetics of RNIB21 in the Treatment of Patients With Irritable Bowel Syndrome With Diarrhea (IBS-D)

This study will see if adding the supplement N-acetylcysteine (NAC) to rifaximin helps adults with IBS-D have less belly pain and firmer stools.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 225 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Cedars-Sinai Medical Center (Academic / other)
• Locations: 1 site (Los Angeles, California)
• Trial ID: NCT06727422 on ClinicalTrials.gov

What this trial studies

This phase 2b, randomized, double-blind, placebo-controlled trial compares two doses of rifaximin combined with NAC versus placebo given three times daily for 14 days in adults with IBS-D. Patients are randomized 1:1:1 and followed through 14 weeks, with the primary evaluation period covering the 28 days after completing therapy. Daily patient-reported outcomes on abdominal pain and stool consistency are collected via REDCap, and a blinded pharmacokinetics subset of 24 patients will provide serial blood samples to characterize rifaximin and NAC levels. The primary endpoint is the proportion of patients who meet responder criteria for both abdominal pain and stool consistency during the 4-week primary evaluation period, per FDA guidance.

Who should consider this trial

Good fit: Adults (≥18) with Rome IV–confirmed IBS-D who have inadequate relief of abdominal pain and abnormal stool consistency (weekly average worst pain >3 and at least one Bristol Type 6–7 stool) are ideal candidates.

Not a fit: Patients with constipation-predominant IBS, inflammatory bowel disease, celiac disease, recent relevant GI surgery, active GI infection, current asthma, pregnant or breastfeeding women, or those unable to attend in-person visits are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, the combination could provide better and longer-lasting relief of abdominal pain and diarrhea symptoms than rifaximin alone.

How similar studies have performed: Rifaximin alone is FDA-approved and has shown benefit for IBS-D, but combining rifaximin with NAC is a novel approach that has not been proven for this condition.

Eligibility criteria

Inclusion Criteria:

1. Male or non-pregnant, non-lactating female patients ≥ 18 years of age
2. Diagnosed with IBS confirmed by the Rome IV criteria, with associated symptoms of diarrhea as noted below in 4(b).
3. Do not have adequate relief of IBS symptoms of abdominal pain, stool consistency or stool frequency
4. Have daily IBS symptom scores during screening as below:

   1. Weekly average score of worst daily abdominal pain \>3.0 on a 0-10 point scale
   2. At least one stool with a consistency of Type 6 or 7 on the Bristol

Exclusion Criteria:

1. Present with the following symptoms of IBS with constipation:

   1. Less than 3 bowel movements a week,
   2. Hard or lumpy stools, and
   3. Excessive straining during a bowel movement.
2. History of inflammatory bowel disease, celiac disease, GI surgery (except cholecystectomy and/or appendectomy)
3. Evidence of active duodenal ulcer, gastric ulcer, diverticulitis, or active infectious gastroenteritis
4. Current diagnosis of asthma
5. Current user of NAC and/or rifaximin
6. Systemic antibiotic use in the last month
7. Not currently on a prokinetic drug
8. A significant medical condition including but not limited to hepatic, uncontrolled diabetes, renal, cardiovascular, pulmonary, uncontrolled thyroid disease. or psychiatric disease, which in the opinion of investigator precludes study participation

Where this trial is running

Los Angeles, California

• Cedars-Sinai Medical Center — Los Angeles, California, United States (Recruiting)

Study contacts

• Study coordinator: Mark Pimentel, MD

Conditions IBS; IBS-D