Efficacy of Rifaximin With NAC in IBS-D

NCT06727422 | Recruiting Phase 2 FDA Drug

• 1 other identifier: RNIB21-201
• Study Type: interventional
• Target: 225
• Locations: 1 country
• Sites: 1

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)

Keywords

IBS-D

Outcome Measures

Primary Outcomes (2)

• stool consistency

  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

  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 Outcomes (2)

• overall response

  up to 7 weeks of 14 weeks

• stool frequency

  2 weeks

Study Arms (3)

low dose for IBS-D

EXPERIMENTAL

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

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

high dose for IBS-D

EXPERIMENTAL

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

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

placebo

PLACEBO COMPARATOR

placebo three times a day

Drug: Placebo

Interventions

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

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

low dose for IBS-D

Placebo DRUG

placebo three times daily

placebo

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

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

high dose for IBS-D

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mark Pimentel, MD: lead

Study Sites (1)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

RECRUITING

Related Publications (21)

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• Pimentel M, Park S, Mirocha J, Kane SV, Kong Y. The effect of a nonabsorbed oral antibiotic (rifaximin) on the symptoms of the irritable bowel syndrome: a randomized trial. Ann Intern Med. 2006 Oct 17;145(8):557-63. doi: 10.7326/0003-4819-145-8-200610170-00004.

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• Sharara AI, Aoun E, Abdul-Baki H, Mounzer R, Sidani S, Elhajj I. A randomized double-blind placebo-controlled trial of rifaximin in patients with abdominal bloating and flatulence. Am J Gastroenterol. 2006 Feb;101(2):326-33. doi: 10.1111/j.1572-0241.2006.00458.x.

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  PMID: 9357184 BACKGROUND

• Pimentel M, Chow EJ, Lin HC. Normalization of lactulose breath testing correlates with symptom improvement in irritable bowel syndrome. a double-blind, randomized, placebo-controlled study. Am J Gastroenterol. 2003 Feb;98(2):412-9. doi: 10.1111/j.1572-0241.2003.07234.x.

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• Agreus L, Svardsudd K, Nyren O, Tibblin G. Irritable bowel syndrome and dyspepsia in the general population: overlap and lack of stability over time. Gastroenterology. 1995 Sep;109(3):671-80. doi: 10.1016/0016-5085(95)90373-9.

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• Hungin AP, Whorwell PJ, Tack J, Mearin F. The prevalence, patterns and impact of irritable bowel syndrome: an international survey of 40,000 subjects. Aliment Pharmacol Ther. 2003 Mar 1;17(5):643-50. doi: 10.1046/j.1365-2036.2003.01456.x.

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• El-Serag HB. Impact of irritable bowel syndrome: prevalence and effect on health-related quality of life. Rev Gastroenterol Disord. 2003;3 Suppl 2:S3-11.

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• Gwee KA, Wee S, Wong ML, Png DJ. The prevalence, symptom characteristics, and impact of irritable bowel syndrome in an asian urban community. Am J Gastroenterol. 2004 May;99(5):924-31. doi: 10.1111/j.1572-0241.2004.04161.x.

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• Bommelaer G, Poynard T, Le Pen C, Gaudin AF, Maurel F, Priol G, Amouretti M, Frexinos J, Ruszniewski P, El Hasnaoui A. Prevalence of irritable bowel syndrome (IBS) and variability of diagnostic criteria. Gastroenterol Clin Biol. 2004 Jun-Jul;28(6-7 Pt 1):554-61. doi: 10.1016/s0399-8320(04)95011-7.

  PMID: 15243388 BACKGROUND

• Pimentel M, Chow EJ, Lin HC. Eradication of small intestinal bacterial overgrowth reduces symptoms of irritable bowel syndrome. Am J Gastroenterol. 2000 Dec;95(12):3503-6. doi: 10.1111/j.1572-0241.2000.03368.x.

  PMID: 11151884 BACKGROUND

Related Links

• Read NW. Irritable Bowel Syndrome. In: Feldman J, Friedman LS, Sleisenger MH, eds. Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management. 7th ed. Philadelphia, PA: Saunders; 2002: 1794-1806.
• Pimentel M. A New IBS Solution: Bacteria - The missing link in treating irritable bowel syndrome. Sherman Oaks, CA: Health Point Press; 2006.

MeSH Terms

Conditions

Irritable Bowel Syndrome

Interventions

Rifaximin; Acetylcysteine

Condition Hierarchy (Ancestors)

Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Central Study Contacts

Mark Pimentel, MD

CONTACT

310.423.0617; mastprogrram@cshs.org

Ava Hosseini

CONTACT

310.423.0617; ava.hosseini@cshs.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: staff physician II

Study Record Dates

• First Submitted: December 5, 2024
• First Posted: December 10, 2024
• Study Start: February 4, 2026
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: April 20, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)