Novel Tracer Methods to Evaluate Muscle Protein Metabolism in Cirrhosis

Study Overview
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Brief Summary
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To determine the rate and mechanisms of skeletal muscle protein synthesis and breakdown in cirrhotic patients by using multiple tracers and single muscle biopsies.

Detailed Description
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The goal of this study is to identify the molecular regulatory mechanisms that result in loss of skeletal muscle in cirrhotic patients. Current strategies involve prolonged tracer infusion and multiple muscle biopsies. We will use an innovative approach to determine the rates of skeletal muscle protein synthesis and breakdown using multiple tracers administered at short intervals followed by a single muscle biopsy. These studies are likely to provide a conceptual advance in determining the cellular and molecular responses of the skeletal muscle in cirrhosis.

Official Title
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Multiple Tracer Using Single Muscle Biopsy Technique in Evaluating Protein Synthesis and Break Down in Muscles of Cirrhotic Patients

Conditions
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Cirrhosis

Intervention / Treatment
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* Procedure: blood draw and muscle biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The diagnosis of cirrhosis based on liver biopsy and/or clinical, biochemical, and imaging criteria. Patients with Child Pugh score from A5- to B7 Control group: Subject in control group should have serum ALT and AST within normal range. Exclusion Criteria for both groups (cirrhotic and control) are: diabetes cancer kidney failure pregnancy recent surgery (bowel resection or Gastric bypass operation) Advanced cardiac or pulmonary disease patient with thyroid disease & Coagulopathy ( INR >1.4 and platelet count <80,000/ml)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with Cirrhosis<br>Patients with a diagnosis of cirrhosis will have a blood draw and muscle biopsy will be performed. | Procedure: blood draw and muscle biopsy<br>* One venous catheter will be used for bolus injection of multiple labeled AA at the beginning .The second venous catheter will inserted in the other arm for 5 ml of arterialized venous blood draw.Following the infusions, a single muscle biopsy will be performed from the vastus lateralis of the thigh using the Bergstromm needle.<br>|
| controls<br>control group should have serum ALT and AST within normal range and a blood draw and muscle biopsy will be performed | Procedure: blood draw and muscle biopsy<br>* One venous catheter will be used for bolus injection of multiple labeled AA at the beginning .The second venous catheter will inserted in the other arm for 5 ml of arterialized venous blood draw.Following the infusions, a single muscle biopsy will be performed from the vastus lateralis of the thigh using the Bergstromm needle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fractional Synthesis Rate | Fractional synthesis rate (FSR)for each patient is measured by the rate of tracer incorporation from the MIF pool to the bound pool. | 4 hours |