HMB Enriched Amino Acids to Reverse Muscle Loss in Cirrhosis

NCT ID: NCT05166499

Last Updated: 2025-11-25

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-30
• Study Completion Date: 2026-12-30

Brief Summary

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.

Conditions

Cirrhosis, Liver

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Hydroxy Methyl Butyrate

Group Type: ACTIVE_COMPARATOR

Hydroxy Methyl Butyrate

Intervention Type: DIETARY_SUPPLEMENT

Hydroxy Methyl Butyrate

Balanced Amino Acid Mixture

Group Type: OTHER

Balanced Amino Acids

Intervention Type: DIETARY_SUPPLEMENT

Balanced Amino Acids

Interventions

Hydroxy Methyl Butyrate

Hydroxy Methyl Butyrate

Intervention Type: DIETARY_SUPPLEMENT

Balanced Amino Acids

Balanced Amino Acids

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

• Diagnosis of cirrhosis of the liver
• Child-Pugh score of 5-8

Exclusion Criteria

• Recent gastrointestinal bleeding (<3m)
• Active infection
• Overt encephalopathy
• Renal failure on dialysis
• Pedal edema
• Uncontrolled diabetes (HbA1C > 7.9mg/dL)
• Advanced cardiac, lung, kidney disease
• Metastatic cancer
• Medications that alter muscle protein metabolism
• Pregnancy
• Recent bowel resection or gastric bypass surgery,
• INR >1.7, platelets <60,000/ml, serum creatinine >2mg/dL
• Medications that interfere with blood clotting

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Cleveland Clinic

OTHER

Sponsor Role: lead

Responsible Party

Srinivasan Dasarathy

Staff

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Cleveland Clinic

Cleveland, Ohio, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Annette Bellar

Role: CONTACT

bellara@ccf.org

2164456268

Facility Contacts

Annette Bellar

Role: primary

Other Identifiers

21-830

Identifier Type: -

Identifier Source: org_study_id