HMB for Denutrition in Patients With Cirrhosis (HEPATIC)

Summary

Cirrhosis is a late stage of hepatic fibrosis caused by many forms of liver diseases and conditions, such as hepatitis and chronic alcoholism. The World Health Organization (WHO) has reported that this condition accounts for 1.8% of all deaths in Europe (170,000 deaths/year).

Patients with cirrhosis are characterized by severe metabolic alterations, which converge in a malnutritional state. Malnutrition encompasses glucose intolerance, chronic inflammation, altered gut microbiota, reduced muscle mass (sarcopenia), as well as loss and dysregulation of adipose tissue (adipopenia). Malnutrition is the most frequent complication that adversely affects the outcomes of cirrhotic patients. Yet, despite its clinical repercussions and potential reversibility, there are no effective therapies because our limited understanding of the mechanisms underlying this altered metabolism.

β-hydroxy β-methylbutyrate (HMB) is a naturally produced substance regarded as safe and effective in preventing muscle loss during chronic diseases. Previous studies have indicated some beneficial effects of HMB itself or its parent metabolite, leucine, on adipose tissue, glucose intolerance, inflammation, and gut microbiota. This study aims to translate those beneficial effects to cirrhotic patients. The investigators hypothesize that HMB can improve cirrhosis-related metabolic abnormalities through its pleiotropic effects. The goals of this study are: i) to perform a randomized clinical trial to evaluate the efficacy of HMB, administered as nutritional supplementation, on clinical symptoms of cirrhosis.

ii) to uncover the precise metabolic pathways that underlie HMB action, with a special focus on muscle, adipose tissue, and gut microbiota.

Conditions

• Sarcopenia
• Cirrhosis
• Malnutrition

Interventions

DIETARY_SUPPLEMENT

Ensure Plus Advance

Supplements, labeled only with the name of the participant and his/her identification number, will be provided to the participants in the Translational Research Unit of the Miguel Servet Hospital. Every 2 weeks, changes in body composition, in particular in fat and muscle, will be assessed by bioelectrical impedance analysis (BIA). Likewise they will be asked about compliance and their diets will be controlled by a nutritionist. Fresh stool samples, urine and blood will be collected pre- and post treatment. An extensive bloodwork will be performed at the Clinical Biochemistry Service at the Miguel Servet Hospital (plasma HMB, total cholesterol, triglycerides, LDL\&HDL-cholesterol, free fatty acids, glucose, insulin, β-hydroxybutyrate, hs-CRP, and liver transaminases (AST, ALT, GGT).

DIETARY_SUPPLEMENT

Ensure High Protein

Supplements, labeled only with the name of the participant and his/her identification number, will be provided to the participants in the Translational Research Unit of the Miguel Servet Hospital. Every 2 weeks, changes in body composition, in particular in fat and muscle, will be assessed by bioelectrical impedance analysis (BIA). Likewise they will be asked about compliance and their diets will be controlled by a nutritionist. Fresh stool samples, urine and blood will be collected pre- and post treatment. An extensive bloodwork will be performed at the Clinical Biochemistry Service at the Miguel Servet Hospital (plasma HMB, total cholesterol, triglycerides, LDL\&HDL-cholesterol, free fatty acids, glucose, insulin, β-hydroxybutyrate, hs-CRP, and liver transaminases (AST, ALT, GGT).

Sponsors & Collaborators

• Refbio2: Trans-Pyrenean cooperation network for biomedical research

  collaborator UNKNOWN

• Instituto Aragones de Ciencias de la Salud

  lead OTHER_GOV

Principal Investigators

• Alejandro Sanz-Paris, MD · Hospital Miguel Servet

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

99 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2017-10-15

Primary Completion

2018-03-31

Completion

2019-12-31

Countries

• Spain

Study Locations