Probiotic Lactobacillus GG (LGG) in Patients With Minimal Hepatic Encephalopathy
Condition: Minimal Hepatic Encephalopathy
MeSH terms: Hepatic Encephalopathy; Brain Diseases
Study type: Interventional
Phase: Phase 1

Summary: 
      This research proposes to find whether the probiotic lactobacillus GG is safe and well
      tolerated in patients with minimal hepatic encephalopathy. We also want to get insight into
      the mechanisms of action of LGG.
    

Detailed description: 
      Development of complementary and alternative medicine approaches to liver disease is a
      priority area at NCCAM. Minimal hepatic encephalopathy (MHE) is a significant complication of
      cirrhosis which can result in poor quality of life, impaired cognition and difficulty in
      driving motor vehicles with a high traffic accident risk. MHE is estimated to affect one half
      of the 5.5 million cirrhotics in the U.S. Despite these negative outcomes, there is no
      consensus on treatment of MHE. Currently available therapies for MHE act on intestinal flora
      but are limited by adverse effects (i.e. lactulose-induced diarrhea), which negatively impact
      adherence. Probiotic bacterial supplements, which also act on intestinal flora, are an
      emerging therapy for MHE. Our group has performed a pilot, randomized trial which
      demonstrated a significantly higher rate of MHE reversal with excellent adherence in patients
      randomized to probiotic yogurt compared to no therapy. This proposal intends to define
      Lactobacillus GG (LGG) as a biologically-based alternative therapy for MHE with special focus
      on metabolic and stool bacteriologic changes.

      The hypothesis of this Phase I proposal is: LGG will be safe and efficacious for the
      treatment of minimal hepatic encephalopathy compared to placebo in a randomized, double-blind
      trial.

      This will be carried out with four specific aims:

      Specific aim 1: To define the safety and tolerability of LGG in patients with minimal hepatic
      encephalopathy against placebo in a Phase I randomized controlled trial.

      Specific aim 2: To define the effect of LGG on intestinal microflora composition in
      cirrhotics with minimal hepatic encephalopathy using 16s stool DNA sequencing in a
      randomized, placebo-controlled trial.

      Specific aim 3: To determine the effect of LGG on metabolic biomarkers and cytokines in
      stool, urine and blood using nuclear magnetic resonance spectroscopy in minimal hepatic
      encephalopathy.

      Specific aim 4: To determine the effect of LGG on psychometric function in patients with
      minimal hepatic encephalopathy.

      The specific aim and sub-aims will be tested in 30 patients with non-alcoholic cirrhosis and
      MHE: 15 randomized to LGG and 15 randomized to placebo to be taken BID for 8 weeks with
      detailed psychometric, metabolic, anthropometric and bacteriologic evaluation. Results
      generated from this study will form the basis for a RO1 proposal to develop the use of
      probiotics as a biologically-based alternative treatment with long-term outcomes of
      prognosis, development of overt encephalopathy and prevention of traffic accidents in
      patients with MHE.
    

Intervention name(s): Lactobacillus GG; Placebo
Intervention type(s): Biological; Biological
Intervention description(s): 1 capsule of lactobacillus GG BID compared to placebo BID; 1 capsule of lactobacillus GG BID compared to placebo BID
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: cirrhosis; hepatic encephalopathy; complications; probiotic; lactobacillus GG