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

Minimal Hepatic Encephalopathy Clinical Trial

Official title:

Probiotic LGG in Patients With Minimal Hepatic Encephalopathy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00992290
• Other study ID #: HM12123
• Secondary ID: 1U01AT004428-01A
• Status: Completed
• Phase: Phase 1
• First received: October 6, 2009
• Last updated: January 6, 2014
• Start date: October 2009
• Est. completion date: March 2013

Study information

• Verified date: January 2014
• Source: Virginia Commonwealth University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: March 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Diseases
• Hepatic Encephalopathy
• Minimal Hepatic Encephalopathy

Intervention

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

Locations

Country	Name	City	State
United States	Virginia Commonwealth University	Richmond	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
Virginia Commonwealth University	National Center for Complementary and Integrative Health (NCCIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of LGG		3 years	Yes
Secondary	Quality of life measured by sickness impact profile		3 years	No
Secondary	Bacteriology measured in the stool flora by specialized non-culture techniques		3 years	No
Secondary	Metabonomics and psychometric testing using a standard psychometric battery		3 years	No