Clinical trial NCT01110447: Secondary Prophylaxis of Hepatic Encephalopathy With a Probiotic Preparation
Official title: Secondary Prophylaxis of Hepatic Encephalopathy: A Double Blind, Randomized, Placebo Controlled Study With Supplementation With a Probiotic Preparation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Hepatic Encephalopathy
Keywords: Hepatic Encephalopathy, probiotics
Lead sponsor: CD Pharma India Pvt. Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Post Graduate Institute of Medical Education and Research, Chandigarh
First posted: 2010-04-26
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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)

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 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.

Primary outcomes:
measure: The primary end point will be development of overt HE or completion of a follow-up of 6 months after enrollment
timeFrame: 6 months after enrollment
Secondary outcomes:
measure: Improvement in liver functions (Child and MELD score), psychometry (psychometric hepatic encephalopathy score), blood ammonia, blood cytokines level and survival time after medication
timeFrame: 6 months after enrollment
Other outcomes:
Locations:
city: Chandigarh
country: India
facility: Dept. of Hepatology, PGIMER
Study officials:
affiliation: Postgraduate Institute of Medical Education & Research (PGIMER)
name: Radha K Dhiman, MD,DM,MNAMS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dhiman RK, Grover GS, Premkumar M, Roy A, Taneja S, Duseja A, Arora S; MMPHCRF Investigators. Outcomes of Real-World Integrated HCV Microelimination for People Who Inject Drugs: An expansion of the Punjab Model. EClinicalMedicine. 2021 Oct 17;41:101148. doi: 10.1016/j.eclinm.2021.101148. eCollection 2021 Nov.
citation: Dhiman RK, Grover GS, Premkumar M, Taneja S, Duseja A, Arora S, Rathi S, Satsangi S, Roy A; MMPHCRF Investigators. Decentralized care with generic direct-acting antivirals in the management of chronic hepatitis C in a public health care setting. J Hepatol. 2019 Dec;71(6):1076-1085. doi: 10.1016/j.jhep.2019.07.006. Epub 2019 Jul 17.
citation: Dhiman RK, Rana B, Agrawal S, Garg A, Chopra M, Thumburu KK, Khattri A, Malhotra S, Duseja A, Chawla YK. Probiotic VSL#3 reduces liver disease severity and hospitalization in patients with cirrhosis: a randomized, controlled trial. Gastroenterology. 2014 Dec;147(6):1327-37.e3. doi: 10.1053/j.gastro.2014.08.031. Epub 2014 Aug 27.