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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

October 6, 2009
January 6, 2014
October 2009
December 2012   (final data collection date for primary outcome measure)
Safety of LGG [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
Tolerability of LGG defined as adherence and adverse effects (as prescribed by the FDA) [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00992290 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Probiotic Lactobacillus GG (LGG) in Patients With Minimal Hepatic Encephalopathy
Probiotic LGG in Patients With Minimal Hepatic Encephalopathy

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.

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.

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Minimal Hepatic Encephalopathy
  • Biological: Lactobacillus GG
    1 capsule of lactobacillus GG BID compared to placebo BID
  • Biological: Placebo
    1 capsule of lactobacillus GG BID compared to placebo BID
  • Experimental: Lactobacillus GG
    Intervention: Biological: Lactobacillus GG
  • Placebo Comparator: Placebo
    Intervention: Biological: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
37
March 2013
December 2012   (final data collection date for primary outcome measure)

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
Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00992290
HM12123, 1U01AT004428-01A1
Yes
Virginia Commonwealth University
Virginia Commonwealth University
National Center for Complementary and Alternative Medicine (NCCAM)
Principal Investigator: Jasmohan S Bajaj, MD, MSc Virginia Commonwealth University
Virginia Commonwealth University
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP