Effects of Proteins in Patients With Cirrhosis and Prior Hepatic Encephalopathy

Effect of the Proteins of the Diet in Patients With Cirrhosis and a Prior Episode of Hepatic Encephalopathy. A Randomized Study

The purpose of this study is to compare a normal-protein diet containing branched-chain amino acids to a low-protein diet in patients with non-terminal cirrhosis (MELD < 25) who have developed an episode of hepatic encephalopathy within two months prior to inclusion.

Study Overview

• Status: Completed
• Conditions: Hepatic Encephalopathy
• Intervention / Treatment: Dietary supplement: Branched-chain amino acids; Dietary supplement: Maltodextrin

Detailed Description

Hepatic encephalopathy is a major complication of cirrhosis associated with poor prognosis and poor quality of life. Appearance of HE occurs in the setting of precipitating factors that increase plasma ammonia. The gastrointestinal tract is the primary source of ammonia, which is produced by enterocytes from glutamine and by colonic bacterial catabolism of nitrogenous sources, such as ingested proteins. This is the rationale for proposing low-protein diet as strategy to reduce ammonia production and as standard diet in patients with cirrhosis and hepatic encephalopathy. However, low-protein diet could cause wasting muscle and predispose to recurrence of hepatic encephalopathy, since muscle is an important site for extrahepatic ammonia removal.

Branched-chain amino acids have shown beneficial effects on mental state of patients with chronic hepatic encephalopathy. The possible mechanism of action may be improvement of nutritional status through induction of protein synthesis. However, role of branched-chain amino acids in treatment and prevention of acute hepatic encephalopathy is not established.

Administration of a normal-protein diet containing oral branched-chain amino acids may reduce recurrence of hepatic encephalopathy as compared to a low-protein diet.

• Study Type: Interventional
• Enrollment (Actual): 116
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Barcelona, Spain, 08025
    • Hospital de Sant Pau
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
      • Corporacio Sanitaria Parc Tauli

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Cirrhosis of the liver.
• Recovery from an episode of hepatic encephalopathy within two months prior to inclusion.
• Compliance with a standard diet during two weeks prior to inclusion.

Exclusion Criteria:

• End-stage cirrhosis (MELD score > 25).
• Marked cognitive disorder (mini-mental test < 27).
• Non-treatable hepatocarcinoma in accordance with Milan criteria.
• Comorbid conditions with a life expectancy less than 6 months.
• Neurological conditions that difficult assessment of treatment of hepatic encephalopathy (dementia, encephalitis, severe depression).
• Diseases requiring administration of a specific diet (malabsorption, chronic diarrhea, chronic pancreatic insufficiency, severe obesity).
• No acceptation of written consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Normal-protein diet; Daily diet containing 35 kcal/kg/day, 0.7 grams of proteins/kg/day + 30 grams of oral branched-chain amino acids (leucine: 13.5 grams, isoleucine: 9 grams, valine: 7.5 grams).	Dietary supplement: Branched-chain amino acids; 30 grams of oral branched-chain amino acids (leucine: 13.5 grams, isoleucine: 9 grams, valine: 7.5 grams) daily
ACTIVE_COMPARATOR: Low-protein diet; Daily diet containing 35 kcal/kg/day, 0.7 grams of proteins/kg/day + 30 grams of oral maltodextrine	Dietary supplement: Maltodextrin; 30 grams of oral maltodextrin daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Hepatic encephalopathy-free survival	56 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall duration in days of episodic hepatic encephalopathy	56 weeks
Minimal hepatic encephalopathy assessed by neuropsychological tests	56 weeks
Health-related quality of life	56 weeks
Nutritional status	56 weeks
Liver function	56 weeks

Collaborators and Investigators

• Sponsor: Hospital Universitari Vall d'Hebron Research Institute

Study record dates

Study Major Dates

• Study Start: January 1, 2003
• Primary Completion (ACTUAL): January 1, 2008
• Study Completion (ACTUAL): January 1, 2009

Study Registration Dates

• First Submitted: July 21, 2009
• First Submitted That Met QC Criteria: August 7, 2009
• First Posted (ESTIMATE): August 10, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): August 10, 2009
• Last Update Submitted That Met QC Criteria: August 7, 2009
• Last Verified: August 1, 2009

More Information

Terms related to this study

• Keywords: Cirrhosis; Hepatic encephalopathy; Branched-chain amino acids; Proteins of the diet
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Failure; Hepatic Insufficiency; Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Liver Diseases; Brain Diseases, Metabolic; Fibrosis; Hepatic Encephalopathy; Brain Diseases
• Other Study ID Numbers: PR(HG)61/2002