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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Virginia Commonwealth University
ClinicalTrials.gov Identifier:
NCT00992290
First received: October 6, 2009
Last updated: January 6, 2014
Last verified: January 2014
  Purpose

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 Intervention Phase
Minimal Hepatic Encephalopathy
Biological: Lactobacillus GG
Biological: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Probiotic LGG in Patients With Minimal Hepatic Encephalopathy

Resource links provided by NLM:


Further study details as provided by Virginia Commonwealth University:

Primary Outcome Measures:
  • Safety of LGG [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Quality of life measured by sickness impact profile [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Bacteriology measured in the stool flora by specialized non-culture techniques [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Metabonomics and psychometric testing using a standard psychometric battery [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Enrollment: 37
Study Start Date: October 2009
Study Completion Date: March 2013
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00992290

Locations
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Virginia Commonwealth University
Investigators
Principal Investigator: Jasmohan S Bajaj, MD, MSc Virginia Commonwealth University
  More Information

No publications provided

Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT00992290     History of Changes
Other Study ID Numbers: HM12123, 1U01AT004428-01A1
Study First Received: October 6, 2009
Last Updated: January 6, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Virginia Commonwealth University:
cirrhosis
hepatic encephalopathy
complications
probiotic
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

ClinicalTrials.gov processed this record on September 22, 2014