Efficacy and Safety of Rifaximin With NAC in IBS-D
Condition: Irritable Bowel Syndrome With Diarrhea
MeSH terms: Irritable Bowel Syndrome; Syndrome; Diarrhea
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

Intervention name(s): Rifaximin; N-acetylcysteine; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Rifaximin is indicated for the treatment of irritable bowel syndrome with diarrhea (IBS-D) in adults.; N-acetylcysteine (NAC) is a clinically approved mucolytic agent.; 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.
Other intervention name(s): xifaxan; NAC
Intervention MeSH terms: Acetylcysteine; Rifaximin; N-monoacetylcystine
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Irritable Bowel Syndrome with Diarrhea; IBS-D; Rifaximin; N-acetylcysteine; NAC