Probiotic Lactobacillus GG (LGG) in Patients With Minimal Hepatic Encephalopathy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00992290
Recruitment Status : Completed
First Posted : October 9, 2009
Last Update Posted : January 7, 2014
National Center for Complementary and Integrative Health (NCCIH)
Information provided by (Responsible Party):
Virginia Commonwealth University

Brief 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.

Condition or disease Intervention/treatment Phase
Minimal Hepatic Encephalopathy Biological: Lactobacillus GG Biological: Placebo Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Probiotic LGG in Patients With Minimal Hepatic Encephalopathy
Study Start Date : October 2009
Actual Primary Completion Date : December 2012
Actual Study Completion Date : March 2013

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Lactobacillus GG Biological: Lactobacillus GG
1 capsule of lactobacillus GG BID compared to placebo BID

Placebo Comparator: Placebo Biological: Placebo
1 capsule of lactobacillus GG BID compared to placebo BID

Primary Outcome Measures :
  1. Safety of LGG [ Time Frame: 3 years ]

Secondary Outcome Measures :
  1. Quality of life measured by sickness impact profile [ Time Frame: 3 years ]
  2. Bacteriology measured in the stool flora by specialized non-culture techniques [ Time Frame: 3 years ]
  3. Metabonomics and psychometric testing using a standard psychometric battery [ Time Frame: 3 years ]

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age: 18-65 years
  • Histological evidence of cirrhosis
  • Maintenance of cirrhosis treatment and stability for 6 months
  • Mini-mental state exam score > 25
  • Presence of MHE on psychometric testing

Exclusion Criteria:

  • Rx for MHE or OHE
  • Antibiotics within 6 weeks
  • Yogurt consumption within 2 weeks
  • Neutrophil count < 500
  • Inflammatory bowel disease
  • History of pancreatitis
  • Hepato-cellular carcinoma
  • Recent (6 weeks) gastrointestinal bleed
  • Recent (6 months) alcohol intake
  • Psychoactive medications (including interferon/antipsychotics)
  • Liver transplant

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00992290

United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Virginia Commonwealth University
National Center for Complementary and Integrative Health (NCCIH)
Principal Investigator: Jasmohan S Bajaj, MD, MSc Virginia Commonwealth University

Responsible Party: Virginia Commonwealth University Identifier: NCT00992290     History of Changes
Other Study ID Numbers: HM12123
1U01AT004428-01A1 ( U.S. NIH Grant/Contract )
First Posted: October 9, 2009    Key Record Dates
Last Update Posted: January 7, 2014
Last Verified: January 2014

Keywords provided by Virginia Commonwealth University:
hepatic encephalopathy
lactobacillus GG

Additional relevant MeSH terms:
Brain Diseases
Hepatic Encephalopathy
Central Nervous System Diseases
Nervous System Diseases
Liver Failure
Hepatic Insufficiency
Liver Diseases
Digestive System Diseases
Brain Diseases, Metabolic
Metabolic Diseases