Effects of Proteins in Patients With Cirrhosis and Prior Hepatic Encephalopathy

Sponsor

Hospital Universitari Vall d'Hebron Research Institute (Other)

Overall Status

Completed

CT.gov ID

NCT00955500

Collaborator

(none)

116

Enrollment

Locations

Arms

Duration (Months)

38.7

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatic Encephalopathy	Dietary Supplement: Branched-chain amino acids Dietary Supplement: Maltodextrin	Phase 4

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 Design

Study Type:

Interventional

Actual Enrollment :

116 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Prevention

Official Title:

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

Study Start Date :

Jan 1, 2003

Actual Primary Completion Date :

Jan 1, 2008

Actual Study Completion Date :

Jan 1, 2009

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Hepatic encephalopathy-free survival [56 weeks]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.