Leucine Enriched Essential Amino Acid Mixture to Reverse Muscle Loss in Cirrhosis

Part of paid clinical trials in Cleveland, Ohio.

Sponsor
The Cleveland Clinic
Study ID
NCT03208868
Status
Recruiting
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Conditions

  • Cirrhosis, Liver

Eligibility Criteria

Sex
ALL
Age
18 Years - 70 Years
Healthy Volunteers
Accepted

Interventions

  • Leucine enriched essential amino acid (EEA/LEU) — DIETARY_SUPPLEMENT
    Patient with cirrhosis will be randomized to either take a Leucine enriched essential amino acid or a balanced amino acid supplement.
  • Balanced amino acid supplement (BAA) — DIETARY_SUPPLEMENT
    Patient with cirrhosis will be randomized to either take a Leucine enriched essential amino acid or a balanced amino acid supplement.

Study Details

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.

Key Dates

Start date
Aug 5, 2013
Status verified
Oct 2025
Primary completion
Dec 31, 2026
Completion
Dec 31, 2026

Study Design

Enrollment
32 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION

Arms

  • Active Comparator: Leucine enriched essential amino acid
    Patients with cirrhosis that are given a leucine enriched essential amino acid (EEA/LEU) supplement.
  • Active Comparator: Balanced amino acid supplement
    Patients with cirrhosis that are given a balanced amino acid (BAA) supplement.

Primary Outcome Measure

Compare Fractional Synthesis Rate [ Time Frame: Baseline to 90 days ]

Locations (1)

FacilityCityStateZIPSite coordinators
Cleveland Clinic FoundationClevelandOhio44195
Annette Bellar, BS
[email protected]
216-636-5247
Revathi Penumatsa, MD
[email protected]
216-445-0688
Srinivasan Dasarathy, MD (PRINCIPAL_INVESTIGATOR)

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By research site
Cleveland Clinic Foundation· Cleveland, OH

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