Secondary Prophylaxis of Hepatic Encephalopathy in Cirrhosis (HE)

Secondary Prophylaxis of Hepatic Encephalopathy in Cirrhosis: An Open Label, Randomized Controlled Trial of Lactulose, Probiotics and No-therapy

Hepatic encephalopathy (HE), a challenging complication of advanced liver disease, occurs in approximately 30-45% of patients with cirrhosis. The treatment of choice is non-absorbable disaccharides, such as lactulose and lactitol.Probiotics are effective in the treatment of minimal hepatic encephalopathy which precipitates hepatic encephalopathy. The investigators will assess the effects of lactulose and probiotics for the prevention of recurrence of HE (secondary prophylaxis) in patients after the recovery of an episode of overt hepatic encephalopathy.

Study Overview

• Status: Unknown
• Conditions: Hepatic Encephalopathy
• Intervention / Treatment: Drug: Lactulose; Drug: Probiotics(VSL#3)

Detailed Description

Hepatic encephalopathy, a challenging complication of advanced liver disease, occurs in approximately 30-45% of patients with cirrhosis and 10-50% of patients with transjugular intrahepatic portosystemic shunt.Although the occurrence of episodes of hepatic encephalopathy appears to be unrelated to the cause of cirrhosis,increases in the frequency and severity of such episodes predict an increased risk of death.A small metaanalysis determined that lactulose and lactitol were equally effective in the treatment of HE.Probiotics alter the gut flora resulting in decreased ammonia production and absorption due to decreased intraluminal pH. Also shown to alter the short chain fatty acid production, & decrease intestinal permeability.Various studies have shown some improvement in either the prevalence of minimal hepatic encephalopathy or results in neuropsychological tests with the use of probiotics.Lactulose and probiotics improves minimal hepatic encephalopathy in cirrhotic patients and it has also been shown that minimal hepatic encephalopathy predisposes the cirrhotic patient to HE.We will assess the effects of lactulose and probiotics for the prevention of recurrence of hepatic encephalopathy (secondary prophylaxis) in patients after the recovery of an episode of overt hepatic encephalopathy.

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110002
      • Recruiting
      • G B Pant Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with cirrhosis and previous history of recovery from hepatic encephalopathy

Exclusion Criteria:

• history of taking lactulose in the past 6 weeks.
• alcohol intake during the past 6 weeks or during follow up
• patients on secondary prophylaxis for spontaneous bacterial peritonitis
• previous TIPS 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.

Study Plan

How is the study designed?

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: lactulose; will receive 30-60 ml of lactulose in 2 or 3 divided doses so that patient passed 2-3 semisoft stools per day	Drug: Lactulose; will receive 30-60 ml of lactulose in 2 or 3 divided doses so that patient passed 2-3 semisoft stools per day
Active Comparator: probiotics	Drug: Probiotics(VSL#3); will receive VSL#3 (110 billion CFU)three times a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
episode of overt hepatic encephalopathy	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
side effects to therapy	6 months

Collaborators and Investigators

• Sponsor: Govind Ballabh Pant Hospital

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Study Completion (Anticipated): September 1, 2010

Study Registration Dates

• First Submitted: August 9, 2010
• First Submitted That Met QC Criteria: August 9, 2010
• First Posted (Estimate): August 10, 2010

Study Record Updates

• Last Update Posted (Estimate): August 10, 2010
• Last Update Submitted That Met QC Criteria: August 9, 2010
• Last Verified: September 1, 2009

More Information

Terms related to this study

• Keywords: probiotics; hepatic encephalopathy; lactulose
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Failure; Hepatic Insufficiency; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Liver Diseases; Brain Diseases, Metabolic; Hepatic Encephalopathy; Brain Diseases; Gastrointestinal Agents; Lactulose
• Other Study ID Numbers: PS002