Probiotic preparation, VSL#3 as a support pharmaceutical therapy in cirrhotic patients for the treatment of minimal hepatic encephalopathy (MHE)

Phase 2/3

Completed

Conditions: Cirrhotic patients with Minimal Hepatic encephalopathy

Registration Number: CTRI/2008/091/000268

Lead Sponsor: CD Pharma India Pvt Ltd

Brief Summary: This is a randomized, double-blind, placebo controlled trial to study supplementation with a probiotic preparation, VSL#3® as a support pharmaceutical therapy in cirrhotic patients for the treatment of minimal hepatic encephalopathy (MHE). The study Period is for24 months from the beginning (recruitment: 18 months; VSL#3® supplementation or placebo: 16 weeks). The study population for screening will comprise 150 adult cirrhotic patients (as per hospital prevalence rates) of which 72 would be enrolled for the study: 50% of the patients with MHE will be randomised to receive VSL#3® and 50% to receive placebo. The dose which each patients will receive is one sachet of VSL#3® or placebo per day for 16 weeks. The primary outcome is the evaluation of the beneficial effects of VSL#3® supplementation in cirrhotic patients assessed by a reduction in MHE prevalence and improvement in cognitive functions assessed by psychometric hepatic encephalopathy score (PHES). The secondary outcomes are as follows: Improvement in health related quality of life (HRQOL) assessed by the SF-36 score, liver and renal functions, prevention of major complications of cirrhosis (overt hepatic encephalopathy, variceal bleeding, spontaneous bacterial peritonitis, and hepatopulmonary syndrome), blood ammonia levels, blood cytokines levels, hospital admissions due to cirrhosis complications and survival time after medication. Physical status evaluations include assessment of PHES and SF-36 scores, venous phlebotomy (for Child class, MELD score, ammonia, PCR, endotoxins, interleukin 1 and 6, tumor necrosis factor alpha), H2 breath test for orocecal transit time and small intestinal bacterial overgrowth and HVPG.

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 0

Inclusion Criteria

1.Male and female patients aged more than 16 years; 2.Diagnosis of cirrhosis based on standard clinical and biochemical criteria and, possibly, biopsy proven; 3.No long-term antibiotic treatment needed 4.Able to provide written informed consent.

Exclusion Criteria

1.Alcohol consumption or substance abuse within the last 3 months2.Overt HE or a history of overt HE3.Renal insufficiency with creatinine greater than 1.5 mg/dL (233 μmol/L)4.Ongoing treatment for HE, including treatment with antibiotics (possible treatments should have been stopped at least one month before)5.Need to take long term antibiotics for any reason6.Pregnant females, or females planning to become pregnant, or nursing7.Patients who are unable or unwilling to provide informed consent8.Patients who are taking benzodiazepines, narcotics, anti-depressants, or anti-psychotic medication (previous medication with these drugs should have stopped by one month or more)9.Patients with history of shunt surgery or transjugular intrahepatic portosystemic shunt (TIPSS) for portal hypertension10.Patients with any other organic brain disease, including dementia from any cause, mental retardation, Wilson?s disease, previous stroke, TIA, etc.11.Severe medical problems such as congestive heart failure, pulmonary disease, neurological or psychiatric disorder, etc., that could influence quality-of-life measurement; 12.Inability to perform NP tests due to bad vision13.Patients with gastrointestinal dysfunction (motility, prior resection/surgery, obstruction)14.Gastrointestinal bleeding within 30 days15.Serious infection (e.g. peritonitis) within 30 days16.Known hepatocellular carcinoma or AFP>400.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The primary outcome is the evaluation of the beneficial effects of supplementation with VSL#3® in cirrhotic patients assessed by a reduction in MHE prevalence and improvement in cognitive functions assessed by psychometric hepatic encephalopathy score (PHES).	16 weeks

Secondary Outcome Measures

Name	Time	Method
Assessment of the beneficial effects of food supplementation with the probiotic preparation VSL#3® on:?Improvement in health related quality of life (HR-QOL) (SF-36 score)?Prevention of major complications of cirrhosis (overt encephalopathy, variceal bleeding, spontaneous bacterial peritonitis, and hepatopulmonary syndrome) ?Liver function ?Renal functions?Improvement in hypoxia?Blood ammonia levels, blood cytokines levels, ?Small intestinal bacterial overgrowth and orocecal transit time?HVPG?Hospital admissions due to cirrhosis complications?Survival time after study medication	16 weeks and 20 weeks

Trial Locations

Locations (1): Dept. of Hepatology
🇮🇳
Chandigarh, CHANDIGARH, India
Dept. of Hepatology
🇮🇳Chandigarh, CHANDIGARH, India
Dr. R K Dhiman
Principal investigator
91-9914209337
rkpsdhiman@hotmail.com