Secondary Prophylaxis of Hepatic Encephalopathy With a Probiotic Preparation

Hepatic Encephalopathy Clinical Trial

— VSL#3  

Official title:

Secondary Prophylaxis of Hepatic Encephalopathy: A Double Blind, Randomized, Placebo Controlled Study With Supplementation With a Probiotic Preparation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01110447
• Other study ID #: MHE2-VSL#3-Ver3_30032010
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: April 23, 2010
• Last updated: December 26, 2013
• Start date: April 2010
• Est. completion date: March 2013

Study information

• Verified date: December 2013
• Source: CD Pharma India Pvt. Ltd.
• Contact: n/a
• Is FDA regulated: No
• Health authority: India: Drugs Controller General of India
• Study type: Interventional

Clinical Trial Summary

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)

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 130
• Est. completion date: March 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Brain Diseases
• Hepatic Encephalopathy

Intervention

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:
• Placebo
Placebo sachets contain corn starch. Dose: 1 sachet per day Duration of treatment: 24 weeks

Locations

Country	Name	City	State
India	Dept. of Hepatology, PGIMER	Chandigarh

Sponsors (2)

Lead Sponsor	Collaborator
CD Pharma India Pvt. Ltd.	Postgraduate Institute of Medical Education and Research

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary end point will be development of overt HE or completion of a follow-up of 6 months after enrollment		6 months after enrollment	No
Secondary	Improvement in liver functions (Child and MELD score), psychometry (psychometric hepatic encephalopathy score), blood ammonia, blood cytokines level and survival time after medication		6 months after enrollment	No