Efficacy of Rifaximin With NAC in IBS-D

April 16, 2026 updated by: Mark Pimentel, MD

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)

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a phase 2b, multi-center, randomized, double-blind, placebocontrolled study of rifaximin in patients with IBS-D. Eligible patients will be randomized (1:1:1) to receive RNIB21 containing rifaximin 66mg + NAC 560mg TID; RNIB21 containing rifaximin 132mg + NAC 560mg TID; or placebo TID. The study will consist of the following phases: Screening Phase; Treatment Phase (Days 1 to 14) which includes the Randomization Visit (Day 1) and visits at Week 1 (Day 7 ± 2) and Week 2 (Day 14 ± 2); and a Follow-up Phase including an End of Study visit at Week 14 (Day 98 ± 3). REDCap, a web-based reporting system will be utilized to capture daily patient reported outcomes as regards abdominal pain and stool consistency. A subset of participating sites will be designated as Pharmacokinetics sites. In a blinded fashion 24 patients (8 from each treatment arm) will participate in PK sampling in order to establish a PK profile and PK parameters for both rifaximin and NAC. Serial blood samples will be collected following first dose and last dose to establish the PK profiles after a single dose, and multiple doses. The primary evaluation period (PEP) will be the 28 days following the completion of therapy. The primary outcome for the study will be adequate relief of IBS symptoms based on FDA guidance during this period, specifically: the proportion of patients who are responders to treatment in both IBS-related abdominal pain AND stool consistency during the 4-week PEP. A patient will be considered a weekly responder if there is adequate relief in their IBS-related symptoms, which is defined as a 30% or greater improvement from their baseline in the weekly average of worst abdominal pain in past 24 hours score AND at least 50% reduction in the number of days in a week with at least one stool that has a consistency of type 6 or 7 compared with their baseline. Responders have to meet both abdominal pain and stool consistency criteria for at least 2 of 4 weeks of the PEP. Abdominal pain will be self-reported on a daily basis using an 11-point (0-10) pain scale. Stool consistency will be self-reported daily by patients based on the Bristol Stool Scale. A smartphone app which captures stool image will be used as an seondary endpoint, and compared to the patients' self-reports of stool consistency recorded on the BSS.

Study Type

Interventional

Enrollment (Estimated)

225

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90048
        • Recruiting
        • Cedars-Sinai Medical Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: low dose for IBS-D
RNIB21 containing rifaximin 66mg + NAC 560mg three times a day
Drug: rifaximin 66mg + N-acetylcysteine 560mg three times daily
RNIB21 containing rifaximin 66mg + N-acetylcysteine 560mg three times daily
Experimental: high dose for IBS-D
RNIB21 containing rifaximin 132mg + NAC 560mg three times a day
Drug: RNIB21 containing rifaximin 132mg + N-acetylcysteine 560mg three times daily
RNIB21 containing rifaximin 132mg + N-acetylcysteine 560mg three times daily
Placebo Comparator: placebo
placebo three times a day
Drug: Placebo
placebo three times daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
stool consistency
Time Frame: 2 weeks
A 50% reduction in the number of days per week with at least one stool consistency of Type 6 or 7 on the BSS compared to baseline, for at least 2 of the 4 weeks of the PEP
2 weeks
Abdominal pain
Time Frame: 2 weeks
Abdominal pain will be self-reported on a daily basis using an 11-point (0-10) pain scale, where 10 represent the highest pain.;A 30% improvement compared to baseline on the weekly average score of worst daily abdominal pain for at least 2 of the 4 weeks of the primary evaluation period .
2 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
overall response
Time Frame: up to 7 weeks of 14 weeks
Overall response: Proportion of patients that achieve a weekly response during at least 50% of the weeks of treatment and follow up (i.e. 7 of 14 weeks
up to 7 weeks of 14 weeks
stool frequency
Time Frame: 2 weeks
Stool frequency as number of bowel movements per day averaged on a weekly basis, versus baseline determined during the PEP
2 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mark Pimentel, MD

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 4, 2026

Primary Completion (Estimated)

August 1, 2026

Study Completion (Estimated)

January 1, 2027

Study Registration Dates

First Submitted

December 5, 2024

First Submitted That Met QC Criteria

December 6, 2024

First Posted (Actual)

December 10, 2024

Study Record Updates

Last Update Posted (Actual)

April 20, 2026

Last Update Submitted That Met QC Criteria

April 16, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RNIB21-201

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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