HMB + Amino Acids for Liver Cirrhosis
Trial Summary
What is the purpose of this trial?
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.
Will I have to stop taking my current medications?
The trial requires that you stop taking medications that alter muscle protein metabolism or interfere with blood clotting.
What data supports the effectiveness of the treatment HMB + Amino Acids for Liver Cirrhosis?
Research shows that HMB (a compound that helps build muscle) can improve muscle strength and liver function in patients with liver cirrhosis, and it may help prevent minimal hepatic encephalopathy (a brain disorder caused by liver disease). However, the effects on muscle mass are not clearly demonstrated, and more studies are needed to confirm these benefits.12345
Is HMB and amino acids treatment safe for humans?
How does the treatment HMB + Amino Acids differ from other treatments for liver cirrhosis?
HMB (beta-hydroxy-beta-methylbutyrate) is unique because it is a derivative of the amino acid leucine and is used to potentially improve muscle mass and strength, which is often reduced in liver cirrhosis. Unlike standard treatments, HMB may help increase certain amino acids in the blood and improve muscle function, although its effects on liver cirrhosis are not yet fully established and may vary.12345
Research Team
Eligibility Criteria
This trial is for individuals with a moderate level of liver cirrhosis, as indicated by a Child-Pugh score of 5-8. Participants must not have had recent severe complications like gastrointestinal bleeding or infections, and should not be on dialysis or have uncontrolled diabetes among other exclusions.Inclusion Criteria
Exclusion Criteria
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
Acute Treatment
Participants receive acute administration of hydroxymethyl butyrate (HMB) enriched essential amino acids
Long-term Treatment
Participants receive long-term administration of hydroxymethyl butyrate (HMB) enriched essential amino acids for 3 months
Follow-up
Participants are monitored for safety and effectiveness after treatment
Treatment Details
Interventions
- Balanced Amino Acids (Amino Acid Supplement)
- Hydroxy Methyl Butyrate (Amino Acid Supplement)
Find a Clinic Near You
Who Is Running the Clinical Trial?
The Cleveland Clinic
Lead Sponsor
David Peter
The Cleveland Clinic
Chief Medical Officer
MD, board-certified in Hospice and Palliative Medicine
Tomislav Mihaljevic
The Cleveland Clinic
Chief Executive Officer since 2018
MD from University of Zagreb School of Medicine