Effects of Proteins in Patients With Cirrhosis and Prior Hepatic Encephalopathy

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Hepatic Encephalopathy

Intervention / Treatment
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* Dietary Supplement: Branched-chain amino acids
* Dietary Supplement: Maltodextrin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Normal-protein diet<br>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<br>* 30 grams of oral branched-chain amino acids (leucine: 13.5 grams, isoleucine: 9 grams, valine: 7.5 grams) daily<br>|
| Active Comparator: Low-protein diet<br>Daily diet containing 35 kcal/kg/day, 0.7 grams of proteins/kg/day + 30 grams of oral maltodextrine | Dietary Supplement: Maltodextrin<br>* 30 grams of oral maltodextrin daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hepatic encephalopathy-free survival |  | 56 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatic encephalopathy, Cirrhosis, Proteins of the diet, Branched-chain amino acids