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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
Virginia Commonwealth University
About
Eligibility
Locations
Arms
Outcomes
Full info

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

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

First Posted
October 6, 2009
Last Updated
January 6, 2014
Sponsor
Virginia Commonwealth University
Collaborators
National Center for Complementary and Integrative Health (NCCIH)
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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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