Rifamycin in Minimal Hepatic Encephalopathy
Condition: Hepatic Encephalopathy; Cirrhosis, Liver
MeSH terms: Hepatic Encephalopathy; Liver Cirrhosis; Brain Diseases
Study type: Interventional
Phase: Phase 2

Summary: 
      This is a randomized double-blind placebo-controlled trial of MHE in patients with cirrhosis
      using rifamycin SV-MMX 600mg BID vs placebo for 30 days with PK, safety, microbiota, brain
      function and brain MRI endpoints.
    

Detailed description: 
      Hepatic encephalopathy (HE) is a highly prevalent neuro-cognitive complication of cirrhosis
      characterized by cognitive dysfunction, and high rate of subsequent mortality and recurrence.
      HE also places a tremendous burden with a relentless increase in inpatient stay duration with
      charges topping $7244.7 million in 20092. There were almost 23,000 hospitalizations for HE in
      2009 and far more patients with HE who are being managed as an outpatient in the US. In the
      NACSELD (North American Consortium for the Study of End-Stage Liver Disease) experience, HE
      in inpatients is an independent risk factor for mortality and the leading cause of
      readmissions in patients with cirrhosis.

      HE has two major phases, covert or minimal HE (MHE), which is only recognized by specialized
      tests and overt HE (OHE), which is clinically obvious. OHE forms the tip of the iceberg,
      while MHE affects as many as 60% of tested patients with cirrhosis.

      MHE is associated with changes in specific cognitive domains that result in altered
      health-related quality of life and daily function. This can promote the development of OHE,
      impair driving and employment, increase falls and is independently associated with a risk of
      hospitalizations and mortality.

      There is an alteration of gut microbial composition and function (bile acid changes,
      endotoxemia and gut metabolic products) in cirrhosis, which worsens with disease progression
      with MHE and OHE. Current treatments for OHE are mostly focused on the gut, including
      lactulose and rifaximin. However, despite extracting a major toll on disease progression,
      there is no current guideline to treat MHE. Prior studies using lactulose and rifaximin have
      been performed in this setting with improvement in brain function, brain MRI changes and
      microbial function. However, these are still not standard of care.

      Rifamycin SV MMX® 200 mg is a gut-specific antibiotic with a long track record of safety that
      has been FDA approved for the treatment of traveler's diarrhea. Unlike rifaximin,
      rifamycin-SV MMX mostly affects the colon, where the bacterial load is much larger than in
      the other parts of the GI tract. The impact of rifamycin on MHE has not been studied to date.
      This is a randomized double-blind placebo-controlled trial of MHE in patients with cirrhosis.
    

Intervention name(s): Rifamycin SV MMX; Placebo
Intervention type(s): Drug; Other
Intervention description(s): Intervention arm; Placebo arm
Other intervention name(s): Aemcolo
Intervention MeSH terms: Rifamycins; Rifamycin SV
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: brain MRI; cognitive testing; microbiota; metabolomics; pharmacokinetics