Probiotic Lactobacillus GG (LGG) in Patients With Minimal Hepatic Encephalopathy
Primary Purpose
Minimal Hepatic Encephalopathy
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Lactobacillus GG
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Minimal Hepatic Encephalopathy focused on measuring cirrhosis, hepatic encephalopathy, complications, probiotic, lactobacillus GG
Eligibility Criteria
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
Sites / Locations
- Virginia Commonwealth University
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Lactobacillus GG
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Safety of LGG
Secondary Outcome Measures
Quality of life measured by sickness impact profile
Bacteriology measured in the stool flora by specialized non-culture techniques
Metabonomics and psychometric testing using a standard psychometric battery
Full Information
NCT ID
NCT00992290
First Posted
October 6, 2009
Last Updated
January 6, 2014
Sponsor
Virginia Commonwealth University
Collaborators
National Center for Complementary and Integrative Health (NCCIH)
1. Study Identification
Unique Protocol Identification Number
NCT00992290
Brief Title
Probiotic Lactobacillus GG (LGG) in Patients With Minimal Hepatic Encephalopathy
Official Title
Probiotic LGG in Patients With Minimal Hepatic Encephalopathy
Study Type
Interventional
2. Study Status
Record Verification Date
January 2014
Overall Recruitment Status
Completed
Study Start Date
October 2009 (undefined)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
March 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Virginia Commonwealth University
Collaborators
National Center for Complementary and Integrative Health (NCCIH)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Minimal Hepatic Encephalopathy
Keywords
cirrhosis, hepatic encephalopathy, complications, probiotic, lactobacillus GG
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
37 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Lactobacillus GG
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Biological
Intervention Name(s)
Lactobacillus GG
Intervention Description
1 capsule of lactobacillus GG BID compared to placebo BID
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
1 capsule of lactobacillus GG BID compared to placebo BID
Primary Outcome Measure Information:
Title
Safety of LGG
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Quality of life measured by sickness impact profile
Time Frame
3 years
Title
Bacteriology measured in the stool flora by specialized non-culture techniques
Time Frame
3 years
Title
Metabonomics and psychometric testing using a standard psychometric battery
Time Frame
3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jasmohan S Bajaj, MD, MSc
Organizational Affiliation
Virginia Commonwealth University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
12. IPD Sharing Statement
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Probiotic Lactobacillus GG (LGG) in Patients With Minimal Hepatic Encephalopathy
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