Secondary Prophylaxis of Hepatic Encephalopathy With a Probiotic Preparation (VSL#3)

This study has been completed.
Sponsor:
Collaborator:
Postgraduate Institute of Medical Education and Research
Information provided by (Responsible Party):
CD Pharma India Pvt. Ltd.
ClinicalTrials.gov Identifier:
NCT01110447
First received: April 23, 2010
Last updated: December 26, 2013
Last verified: December 2013
  Purpose

The aim of the proposed project is to study the effects of a probiotic preparation (VSL#3®) for the prevention of recurrence of HE (Hepatic encephalopathy) in patients after the recovery of an episode of overt HE (secondary prophylaxis)


Condition Intervention Phase
Hepatic Encephalopathy
Drug: VSL#3
Other: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Secondary Prophylaxis of Hepatic Encephalopathy: A Double Blind, Randomized, Placebo Controlled Study With Supplementation With a Probiotic Preparation

Resource links provided by NLM:


Further study details as provided by CD Pharma India Pvt. Ltd.:

Primary Outcome Measures:
  • The primary end point will be development of overt HE or completion of a follow-up of 6 months after enrollment [ Time Frame: 6 months after enrollment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Improvement in liver functions (Child and MELD score), psychometry (psychometric hepatic encephalopathy score), blood ammonia, blood cytokines level and survival time after medication [ Time Frame: 6 months after enrollment ] [ Designated as safety issue: No ]

Enrollment: 130
Study Start Date: April 2010
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: VSL#3
VSL#3® is made up of 4 strains of Lactobacilli (L. paracasei, L. plantarum, L. acidophilus and L. delbrueckii subsp. bulgaricus), 3 strains of Bifidobacteria (B. longum, B. infantis, B. breve) and 1 strain of Streptococcus thermophilus.
Drug: VSL#3
VSL#3® is made up of 4 strains of Lactobacilli (L. paracasei, L. plantarum, L. acidophilus and L. delbrueckii subsp. bulgaricus), 3 strains of Bifidobacteria (B. longum, B. infantis, B. breve) and 1 strain of Streptococcus thermophilus. Dose would be 1 sachet per day (Each sachet containing 900 Billion CFU). The duration of treatment would be for 24 weeks
Other Name: Probiotic
Placebo Comparator: Placebo
Placebo sachets contain corn starch
Other: Placebo
Placebo sachets contain corn starch. Dose: 1 sachet per day Duration of treatment: 24 weeks
Other Name: Dummy Preparation

Detailed Description:

Hepatic encephalopathy (HE) represents a spectrum of neuropsychiatric abnormalities seen in patients with liver dysfunction after exclusion of other known brain disease. The Working Party at the 11th World Congress of Gastroenterology, Vienna proposed a multi-axial definition of HE that defined both, the type of hepatic abnormality (type A, B or C) and the duration/characteristics of neurological manifestations (episodic, persistent or minimal HE) in chronic liver disease. Overt hepatic encephalopathy occurs in 30%-45% of cirrhotic patients and 10%-50% of patients with transjugular intrahepatic portosystemic shunt. Development of HE is associated with a poor prognosis. Bustamante et al reported the survival probability of 42% at 1 year of follow-up and 23% at 3 years in patients with cirrhosis with a first episode of acute HE. The primary treatment of HE is the identification and treatment of the precipitating factors. The majority of the drugs used in the treatment of HE are primarily directed at the reduction or elimination of the increased neurotoxic ammonia levels. A meta-analysis of 22 randomized trials highlighted the lack of data supporting the efficacy of nonabsorbable disaccharides; however, the investigators concluded that current evidence is insufficient to support or refute the use of nonabsorbable disaccharides for treatment of HE. Recent studies with well defined groups however demonstrated the efficacy of lactulose. Alternative therapies such as benzodiazepine receptor antagonists, branched-chain amino acids, and L-ornithine-L-aspartate also have been shown to have some role. Antibiotics are effective in the treatment of HE, but adverse effects and concerns about long-term safety have limited their widespread use. Probiotics may have multiple beneficial effects in the prevention and/or treatment of HE. All four published studies on the effect of probiotics on hepatic encephalopathy have demonstrated efficacy. Treating patients to prevent development of a first episode is classified as primary prophylaxis of HE and preventing recurrence of HE in patients who had a previous episode of HE as secondary prophylaxis of HE. Sharma et al recently demonstrated that lactulose is effective in secondary prevention of HE. This study will assess the effects of a probiotic preparation for the prevention of recurrence of HE (secondary prophylaxis) in patients after the recovery of an episode of overt HE.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients diagnosed as having cirrhosis of liver at the Inpatient/Outpatient Liver Clinic of Department of Hepatology, PGIMER, Chandigarh, will be candidates for enrollment.
  • The diagnosis of cirrhosis of liver will be based on clinical, biochemical, and ultrasonographical or liver histological data.

Exclusion Criteria:

  • Alcohol intake during the past 6 weeks
  • Hepatocellular carcinoma
  • Previous transjugular intrahepatic portosystemic shunt or shunt surgery
  • Significant comorbid illness such as heart, respiratory, or renal failure
  • Any neurologic diseases such as Alzheimer's disease, Parkinson's disease, and nonhepatic metabolic encephalopathies.
  • Patients on psychoactive drugs, such as antidepressants or sedatives
  • Those who restart alcohol consumption during follow-up will also be excluded.
  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: NCT01110447

Locations
India
Dept. of Hepatology, PGIMER
Chandigarh, India, 160012
Sponsors and Collaborators
CD Pharma India Pvt. Ltd.
Postgraduate Institute of Medical Education and Research
Investigators
Principal Investigator: Radha K Dhiman, MD,DM,MNAMS Postgraduate Institute of Medical Education & Research (PGIMER)
  More Information

No publications provided

Responsible Party: CD Pharma India Pvt. Ltd.
ClinicalTrials.gov Identifier: NCT01110447     History of Changes
Other Study ID Numbers: MHE2-VSL#3-Ver3_30032010
Study First Received: April 23, 2010
Last Updated: December 26, 2013
Health Authority: India: Drugs Controller General of India

Keywords provided by CD Pharma India Pvt. Ltd.:
Hepatic Encephalopathy, probiotics

Additional relevant MeSH terms:
Hepatic Encephalopathy
Brain Diseases
Liver Failure
Hepatic Insufficiency
Liver Diseases
Digestive System Diseases
Brain Diseases, Metabolic
Central Nervous System Diseases
Nervous System Diseases
Metabolic Diseases

ClinicalTrials.gov processed this record on August 28, 2014