NCT05166499

HMB Enriched Amino Acids to Reverse Muscle Loss in Cirrhosis

Recruiting now NA Last updated 25 November 2025

What this trial tests

NA trial testing Hydroxy Methyl Butyrate in Cirrhosis, Liver in 24 participants. Currently enrolling.

Timeline

30 November 2021

Primary endpoint
30 December 2026

30 December 2026

Quick facts

Lead sponsor	The Cleveland Clinic
Phase	NA
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	other
Enrollment	24
Start date	30 November 2021
Primary completion	30 December 2026
Estimated completion	30 December 2026
Sites	1 location across United States

Drugs / interventions tested

• Hydroxy Methyl Butyrate
• Balanced Amino Acids

Conditions studied

• Cirrhosis, Liver — all drugs for Cirrhosis, Liver →

Sponsor

The Cleveland Clinic

Who can join

Adults 21 to 65, any sex, with Cirrhosis, Liver. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Loss of skeletal muscle mass or sarcopenia is the most common and potentially reversible complication in cirrhosis that increases morbidity and mortality before, during and after liver transplantation. No proven treatments exist for the prevention or reversal of sarcopenia in cirrhosis, primarily because the mechanisms responsible for this are unknown. Based on compelling preliminary studies and those of the co investigator, investigators hypothesize that the mechanism of reduced skeletal muscle mass in cirrhosis is due to a myostatin mediated impaired mTOR (mechanistic target of rapamycin) signaling resulting in reduced protein synthesis and increased autophagy. Investigators further postulate that leucine, a direct stimulant of mTOR, will reverse the impaired mTOR phosphorylation in the skeletal muscle of cirrhotics. The consequent increase in protein synthesis reduced autophagy will result in an increase in skeletal muscle mass. Investigators will test these hypotheses by quantifying the response to acute and long term (3 month) administration of hydroxymethyl butyrate (HMB) enriched essential amino acid compared with an isonitrogenous isocaloric non-essential balanced amino acid mixture (does not stimulate protein synthesis) in cirrhotic patients. Fractional protein synthesis rate (FSR) in skeletal muscle, responses of the molecular regulatory pathways of skeletal muscle protein synthesis, and autophagy flux will be quantified in the acute and long term protocols. Tracer studies using L-\[D5\]-phenylalanine (Phe) as a primed constant infusion (prime 2µmol.kg-1.hr-1; constant 0.05 µmol.kg-1.hr-1) with and L \[ring-D2\] tyrosine, forearm plethysmography, and sequential skeletal muscle biopsies (total of 3 per study subject) will be used to quantify these outcomes. Anthropometric, clinical and body composition measures will be additional outcome measures for the long term intervention. Expression of regulatory signaling proteins, myostatin, IGF-1 (insulin like growth factor) , phospho-Akt, phospho-AMPK (activated protein kinase), phospho-mTOR and phospho-p70s6k will be quantified by Western immunoblots. Autophagy flux will be measured by quantifying expression of the autophagosome proteins.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Treatment of liver fibrosis: Past, current, and future.
   Zhang CY, Liu S, Yang M. · · 2023 · cited 49× · PMID 37397931 · DOI 10.4254/wjh.v15.i6.755
2. Sarcopenia in chronic kidney disease: from bench to bedside.
   Kim DW, Song SH. · · 2023 · cited 18× · PMID 37077132 · DOI 10.3904/kjim.2022.338