Probiotic Lactobacillus GG (LGG) in Patients With Minimal Hepatic Encephalopathy
Probiotic LGG in Patients With Minimal Hepatic Encephalopathy
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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-
Virginia
-
Richmond, Virginia, United States, 23298
- Virginia Commonwealth University
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Placebo Comparator: Placebo
|
1 capsule of lactobacillus GG BID compared to placebo BID
|
|
Experimental: Lactobacillus GG
|
1 capsule of lactobacillus GG BID compared to placebo BID
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Safety of LGG
Time Frame: 3 years
|
3 years
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Quality of life measured by sickness impact profile
Time Frame: 3 years
|
3 years
|
|
Bacteriology measured in the stool flora by specialized non-culture techniques
Time Frame: 3 years
|
3 years
|
|
Metabonomics and psychometric testing using a standard psychometric battery
Time Frame: 3 years
|
3 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Jasmohan S Bajaj, MD, MSc, Virginia Commonwealth University
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- HM12123
- 1U01AT004428-01A1 (U.S. NIH Grant/Contract)
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