Effects of Proteins in Patients With Cirrhosis and Prior Hepatic Encephalopathy

Vall d'Hebron University Hospital (HUVH)

Status and phase: Completed; Phase 4

Conditions: Hepatic Encephalopathy

Treatments: Dietary Supplement: Branched-chain amino acids; Dietary Supplement: Maltodextrin

Study type: Interventional

Funder types: Other

Identifiers

NCT00955500

PR(HG)61/2002

Details and patient eligibility

About

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.

Full 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.

Enrollment: 116 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No 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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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116 participants in 2 patient groups

Normal-protein diet

Active Comparator group

Description:

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).

Treatment:

Dietary Supplement: Branched-chain amino acids

Low-protein diet

Active Comparator group

Description:

Daily diet containing 35 kcal/kg/day, 0.7 grams of proteins/kg/day + 30 grams of oral maltodextrine

Treatment:

Dietary Supplement: Maltodextrin