Probiotic Lactobacillus GG (LGG) in Patients With Minimal Hepatic

Status Completed

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.

Clinical Trial 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 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

Clinical Trial Details

NCT number	NCT00992290
Study type	Interventional
Source	Virginia Commonwealth University
Contact
Status	Completed
Phase	Phase 1
Start date	October 2009
Completion date	March 2013

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See also
Status	Clinical Trial	Phase
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Completed	`NCT04058327` - A Study of MHE in Patients With Liver Diseases
Completed	`NCT02767622` - Reversibility of Minimal Hepatic Encephalopathy Following Liver Transplantation	N/A
Completed	`NCT03585257` - HEAL STUDY (Hepatic Encephalopathy and Albumin Study)	Phase 2
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Completed	`NCT02520817` - Antioxidants and Zinc Improving Minimal Hepatic Encephalopathy In Truck Drivers; a Pilot Study	N/A
Terminated	`NCT00811434` - Study of Lactulose in Children With Chronic Liver Disease	Phase 2
Completed	`NCT00375375` - Effect of Lactulose on Minimal Hepatic Encephalopathy and Health-Related Quality of Life	Phase 4
Completed	`NCT04077125` - Transcranial Doppler Ultrasound and Minimal Hepatic Encephalopathy
Completed	`NCT01069133` - Study of Rifaximin in Minimal Hepatic Encephalopathy	Phase 1/Phase 2
Completed	`NCT01847651` - Brain Muscle Axis During Treatment of Hepatic Encephalopathy With L-ornithine L-aspartate	Phase 4
Completed	`NCT01135628` - Hyperproteic Diet Plus Lactobacillus Reuteri and Nitazoxanide in Minimal Hepatic Encephalopathy	N/A
Completed	`NCT01223729` - Acetyl-L-Carnitine Reduces Depression and Improves Quality of Life in Patients With Minimal Hepatic Encephalopathy	N/A

Clinical trials are conducted in a series of steps, called phases - each phase is designed to answer a separate research question.

Phase 1: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
Phase 2: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.
Phase 3: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
Phase 4: Studies are done after the drug or treatment has been marketed to gather information on the drug's effect in various populations and any side effects associated with long-term use.

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

Clinical Trial Summary

Clinical Trial Description

Study Design

Related Conditions & MeSH terms