Recruiting

Phase 2

Rifaximin & NACEfficacy of Rifaximin With NAC in IBS-D

Sponsor:

Mark Pimentel, MD

Code:

NCT06727422

Conditions

IBS (Irritable Bowel Syndrome)

IBS-D (Diarrhea-predominant)

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

rifaximin 66mg + N-acetylcysteine 560mg three times daily

RNIB21 containing rifaximin 132mg + N-acetylcysteine 560mg three times daily

Placebo

Study Details

Brief 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.

Conditions

IBS (Irritable Bowel Syndrome)

IBS-D (Diarrhea-predominant)

Study ID

NCT06727422

Start date

Feb 4, 2026

Status verified date

Apr, 2026

Completion date

Jan 1, 2027

Anticipated

Primary completion date

Aug 1, 2026

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

225 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: low dose for IBS-D

RNIB21 containing rifaximin 66mg + NAC 560mg three times a day

experimental: high dose for IBS-D

RNIB21 containing rifaximin 132mg + NAC 560mg three times a day

placebo comparator: placebo

placebo three times a day

Interventions

rifaximin 66mg + N-acetylcysteine 560mg three times daily

RNIB21 containing rifaximin 66mg + N-acetylcysteine 560mg three times daily

RNIB21 containing rifaximin 132mg + N-acetylcysteine 560mg three times daily

Placebo

placebo three times daily

Primary outcome measure

stool consistency [ Time Frame: 2 weeks ]
Abdominal pain [ Time Frame: 2 weeks ]

Central Contacts and Locations

Central contacts

Mark Pimentel, MD

310.423.0617 mastprogrram@cshs.org

Ava Hosseini

310.423.0617 ava.hosseini@cshs.org

Locations

Cedars-Sinai Medical Center

Recruiting

Los Angeles, California, United States, 90048

Contacts

Ava Hosseini

3104230617 ava.hosseini@cshs.org

More Information

Sponsor

Mark Pimentel, MD

Last update posted

Apr 20, 2026

Last verified

Apr, 2026

Keywords

IBS-D

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Mark Pimentel, MD on 2026-04-20.