NCT04557215

Efficacy and Safety of Rifaximin With NAC in IBS-D

Evaluation of the Efficacy and Safety of Rifaximin in Combination With N-acetylcysteine (NAC) in Adult Patients With Irritable Bowel Syndrome With Diarrhea

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 45 (actual)
• Sponsor: Cedars-Sinai Medical Center · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

Randomized, prospective proof of concept, double-blind, single site clinical trial to determine the efficacy of combined rifaximin and N-acetylcysteine (NAC) therapy vs. rifaximin alone in decreasing clinical symptoms in subjects with IBS-D.

Detailed description

Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, affecting 11% of the world's population, and accounting for 50% of all gastrointestinal office visits. IBS can be a chronic, long-term condition, with up to 57% of subjects who otherwise had normal bowel function continuing to have altered bowel function for at least 6 years after recovering from the initial acute illness. As a result, the health care costs of IBS have been estimated at over $30 billion per year. Further, this results in serious quality of life implications, which have been likened to diabetes or heart disease, in young adults who should otherwise be productive and healthy. IBS is characterized by abdominal pain, cramping and bloating, accompanied by altered bowel habits. The major forms of IBS are diarrhea-predominant (IBS-D), constipation-predominant (IBS-C) and mixed IBS (IBS-M). There is significant bacterial involvement in IBS, particularly IBS-D. IBS-D can be precipitated by acute gastroenteritis, which is caused by infection with bacterial pathogens such as Escherichia coli, Salmonella, Shigella and Campylobacter jejuni. In addition, there is now overwhelming evidence that small intestinal bacterial overgrowth (SIBO) contributes to the symptoms of IBS-D. Therefore, antibiotic treatment has become a mainstay in the treatment of IBS. Of these, rifaximin is the only antibiotic currently approved by the FDA for the treatment of IBS-D. Rifaximin is an oral, broad-spectrum antimicrobial agent that is minimally absorbed (99.6% retained in the gut), targets the gastrointestinal tract, and associated with a low risk of clinically relevant bacterial antibiotic resistance. It is generally recognized as having no side effects in blinded comparisons that differ from placebo. In two identically designed, phase 3, double-blind, placebo-controlled trials of patients with IBS-D, 40.7% of patients treated with rifaximin 550 mg 3 times daily for 2 weeks experienced adequate relief of global IBS symptoms, compared with 31.7% of patients treated with placebo (P\<0.001). In addition, a greater percentage of rifaximin-treated than placebo-treated patients reported durable improvement in IBS-D symptoms for at least 10 weeks post-treatment. It is well known that treatment of IBS-D with rifaximin is effective and now FDA-approved. However, only 44% of subjects improved with rifaximin treatment. Although what is unique about rifaximin is its 'one-and-done' treatment effect, this is only seen in 36% of subjects who respond to this drug. As such, there is room for improvement with rifaximin. In recent studies, we have shown that the most predominant bacteria in the bacterial overgrowth associated with IBS are E. coli and Klebsiella. Rifaximin is highly effective in treating these two organisms. However, we have since learned that the majority of these excessive organisms in IBS are found in the small intestinal mucus layer. Since rifaximin is not soluble in mucus, it cannot penetrate and affect bacteria within the mucus layer. Our hypothesis that the addition of a mucolytic like N-acetylcysteine (NAC) will allow the penetration of rifaximin into the mucus by first solubilizing rifaximin and secondly liquifying the mucus. This may allow for two important effects. One is a reduction in the necessary dose of rifaximin necessary to treat IBS, and the other is improved efficacy. Both of these will be tested in this trial. In this study, we propose to test whether combining rifaximin with a clinically approved mucolytic agent, NAC, can result in improvement in stool form and reduction in stool frequency, as well as improved relief of clinical symptoms, in subjects with IBS-D.

Conditions

• Irritable Bowel Syndrome With Diarrhea

Interventions

Type	Name	Description
DRUG	Rifaximin	Rifaximin is indicated for the treatment of irritable bowel syndrome with diarrhea (IBS-D) in adults.
DRUG	N-acetylcysteine	N-acetylcysteine (NAC) is a clinically approved mucolytic agent.
DRUG	Placebo	An inactive substance or treatment that looks the same as, and is given in the same way as, an active drug or intervention/treatment being studied.

Timeline

• Start date: 2020-11-13
• Primary completion: 2021-08-31
• Completion: 2022-10-30
• First posted: 2020-09-21
• Last updated: 2023-03-28
• Results posted: 2023-03-28

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study