RecruitingPhase 2NCT06727422

Efficacy of Rifaximin With NAC in IBS-D

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)

Sponsor

Mark Pimentel, MD

Enrollment

225 participants

Start Date

Feb 4, 2026

Study Type

INTERVENTIONAL

Conditions

IBS - Irritable Bowel Syndrome IBS-D (Diarrhea-predominant)

Summary

The purpose of this study is to examine the effectiveness of using a combination of a drug, rifaximin and a dietary supplement, N-acetyl-L-cysteine (NAC), to treat patients with irritable bowel syndrome with diarrhea (IBS-D). Rifaximin is one of the standard treatments for IBS-D and is FDA approved. While rifaximin is safe and effective for treating symptoms in patients with IBS-D, many patients find that their symptoms may not completely resolve, or may come back after a period of time. This research study is designed to test the investigational use of a combination of rifaximin and NAC. The combination of rifaximin and NAC is not approved by the U.S. Food and Drug Administration (FDA) for the treatment of IBS-D, and the effects of taking both medications together are unknown. However, the two medications are approved for use separately, as detailed below. Rifaximin is the only antibiotic approved by the FDA for the treatment of IBS-D. Rifaximin (at a dose of 550 mg by mouth three times daily for 14 days) is approved by the FDA for the treatment of IBS-D. Rifaximin (at a dose of 200 mg per mouth three times daily for 3 days) is FDA approved for the treatment of traveler's diarrhea. Rifaximin at a dose of 200 mg per mouth three times daily is not approved by the FDA for the treatment of IBS-D. NAC is approved by the FDA to treat acetaminophen overdose (72-hour oral and 21-hour intravenous (IV) regimens), and for use in breaking up mucus in the lungs in patients with chronic obstructive pulmonary disease (COPD) and other lung conditions such as bronchitis. NAC is also available over-the-counter in 600 mg and 900 mg capsules as a dietary supplement, although over-the-counter use is not regulated by the FDA. This study will utilize the 600 mg dietary supplement capsules. The Investigators want to know if using a combination of rifaximin and NAC will give better results in decreasing IBS-D symptoms than using rifaximin alone. As NAC is used to break up mucus in the lungs, and the Investigators want to see if this can also break up the mucus layer in the small intestine, and therefore potentially increase the effectiveness of rifaximin. The Investigators will be testing 2 doses to determine which dose is most effective. participants are being asked to take part in this research study because participants were diagnosed with IBS-D.

Eligibility

Min Age: 18 Years

Inclusion Criteria6

Male or non-pregnant, non-lactating female patients ≥ 18 years of age
Diagnosed with IBS confirmed by the Rome IV criteria, with associated symptoms of diarrhea as noted below in 4(b).
Do not have adequate relief of IBS symptoms of abdominal pain, stool consistency or stool frequency
Have daily IBS symptom scores during screening as below:
Weekly average score of worst daily abdominal pain >3.0 on a 0-10 point scale
At least one stool with a consistency of Type 6 or 7 on the Bristol

Exclusion Criteria11

Present with the following symptoms of IBS with constipation:
Less than 3 bowel movements a week,
Hard or lumpy stools, and
Excessive straining during a bowel movement.
History of inflammatory bowel disease, celiac disease, GI surgery (except cholecystectomy and/or appendectomy)
Evidence of active duodenal ulcer, gastric ulcer, diverticulitis, or active infectious gastroenteritis
Current diagnosis of asthma
Current user of NAC and/or rifaximin
Systemic antibiotic use in the last month
Not currently on a prokinetic drug
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