Novel Tracer Methods to Evaluate Muscle Protein Metabolism in Cirrhosis

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

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

Study Overview

• Status: Recruiting
• Conditions: Cirrhosis
• Intervention / Treatment: Procedure: blood draw and muscle biopsy

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

• Study Contact: Name: Annette Bellar, MSLA; Phone Number: 2164450688; Email: bellara@ccf.org

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic Foundation
      • Contact: Annette Bellar, MSLA; Phone Number: 216-445-0688; Email: bellara@ccf.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Study population: Adults with the diagnosis of cirrhosis will be recruited from the hepatology inpatient service, outpatient clinics and liver transplant clinics at the Cleveland Clinic Foundation. The diagnosis of cirrhosis will be based on liver biopsy and/or clinical, biochemical, and imaging criteria. Will include patient with Child Pugh score from A5- to B7

Description

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)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with Cirrhosis; Patients with a diagnosis of cirrhosis will have a blood draw and muscle biopsy will be performed.	Procedure: blood draw and muscle biopsy; 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.
controls; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Investigators: Principal Investigator: Srinivasan Dasarathy, MD, The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start (Actual): July 3, 2017
• Primary Completion (Estimated): September 30, 2024
• Study Completion (Estimated): September 30, 2024

Study Registration Dates

• First Submitted: April 17, 2017
• First Submitted That Met QC Criteria: July 20, 2017
• First Posted (Actual): July 21, 2017

Study Record Updates

• Last Update Posted (Actual): September 14, 2023
• Last Update Submitted That Met QC Criteria: September 13, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis
• Other Study ID Numbers: 14-1476

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No