Leucine Enriched 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 leucine enriched essential amino acid (EAA/LEU) 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 does not specify if you need to stop taking your current medications, but it excludes those taking medications like anabolic steroids or corticosteroids that affect muscle mass.
What data supports the effectiveness of the treatment Leucine Enriched Amino Acids for Liver Cirrhosis?
Research suggests that branched-chain amino acids (BCAAs), which include leucine, may help improve protein metabolism and nutritional status in patients with liver cirrhosis. Some studies indicate that BCAA supplements can enhance protein synthesis and improve nutritional parameters, potentially benefiting patients with cirrhosis.12345
Is leucine-enriched amino acid supplementation safe for humans?
How is the treatment with leucine enriched amino acids different from other treatments for liver cirrhosis?
This treatment is unique because it uses leucine, a branched-chain amino acid, to help improve protein metabolism and nutritional status in patients with liver cirrhosis, which is not typically addressed by standard treatments. Leucine activates specific signals in the body that promote protein synthesis and improve glucose metabolism, offering a novel approach to managing the condition.810111213
Research Team
Eligibility Criteria
This trial is for individuals with liver cirrhosis, confirmed by biopsy or other methods, who have a moderate level of disease severity (Child's Pugh score 5-9) and have not consumed alcohol or recreational drugs for at least six months. People with severe cirrhosis, swelling in the legs, other serious illnesses, diabetes, recent bleeding from the gut, brain issues due to liver disease, kidney failure or certain cancers can't join.Inclusion Criteria
Exclusion Criteria
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
Acute Treatment
Participants receive acute administration of leucine enriched essential amino acid (EAA/LEU) or balanced amino acid (BAA) supplement
Long-term Treatment
Participants receive long-term administration of leucine enriched essential amino acid (EAA/LEU) or balanced amino acid (BAA) supplement
Follow-up
Participants are monitored for safety and effectiveness after treatment
Treatment Details
Interventions
- Balanced amino acid supplement (BAA) (Behavioural Intervention)
- Leucine enriched essential amino acid (EEA/LEU) (Amino Acid Supplement)
Leucine enriched essential amino acid (EEA/LEU) is already approved in Canada, Japan, China for the following indications:
- Nutritional supplement
- Food additive
- Nutritional supplement
Find a Clinic Near You
Who Is Running the Clinical Trial?
The Cleveland Clinic
Lead Sponsor