Ethanol Induces Skeletal Muscle Autophagy

Mechanisms of Skeletal Muscle Proteolysis With Ethanol Consumption: an Integrated Molecular Metabolic Approach

In this study we plan to demonstrate that ethanol induces skeletal muscle autophagy to degrade MAA adducts.

Study Overview

• Status: Recruiting
• Conditions: Alcoholic Liver Disease
• Intervention / Treatment: Other: Biopsies

Detailed Description

Hypothesis: Ethanol mediated modification of skeletal muscle proteins to form MAA adducts that in turn induce skeletal muscle autophagy.

Patients with alcoholic steatosis, hepatitis and cirrhosis (n=10 each) will be recruited from the liver transplant nutrition clinic or the hepatology inpatient service and their body composition quantified using anthropometry, bioelectrical impedance analysis, CT image analysis and DEXA if available.

Control Subjects. Controls will be recruited by advertisement. All control subjects will have a normal clinical history, physical examination, and screening chemistries. They will not have any significant medical conditions requiring the use of medications. Their nutritional status within 20% of normal as defined by ideal body weight.

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Revathi Penumatsa, MPH; Phone Number: 2164450688; Email: penumar@ccf.org
• Study Contact Backup: Name: Annette Bellar, MSLA; Phone Number: 2166365247; Email: bellara@ccf.org

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
      • Contact: Revathi Penumatsa; Phone Number: 216-445-0688; Email: penumar@ccf.org
      • Contact: Annette Bellar; Phone Number: 2166365247; Email: bellara@ccf.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Histologically characterized patients with alcoholic steatosis, hepatitis and cirrhosis (n=10 each) will be recruited from the liver transplant nutrition clinic or the hepatology inpatient service and their body composition quantified using protocols already established by the PI.

Description

Inclusion Criteria:

Alcoholic liver disease:

• clinical, biochemical, imaging criteria and liver biopsy where available
• Age 18 - 65 years old

Controls:

• Serum liver transaminases (i.e. ALT and AST) 40 IU/L
• Normal liver ultrasound
• Age 18 - 65 years old

Exclusion Criteria:

For both groups - alcoholic liver disease and controls:

• Poorly controlled diabetes mellitus (HbA1C>9.5 g/dl)
• Untreated Hyper- / hypo- thyroidism
• Patients on dialysis, renal disease with serum creatinine 1.5 mg/dL
• Active intravenous drug use
• History of bowel surgery or gastric bypass surgery
• Medications known to alter muscle protein metabolism (i.e. corticosteroids, tamoxifen, high-dose estrogen, testosterone or anabolic steroids)
• Metastatic disease, Advanced cardiac or pulmonary disease
• Pregnancy
• Coagulopathy- INR >1.4 and platelet count <80,000/ml.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Alcoholic Steatosis; This group will have 10 patients with alcoholic steatosis which is milder disease and muscle biopsies will be performed	Other: Biopsies; Biopsy will be done on the Vastus Lateralis muscle in all groups
Cirrhosis; This group will consist of 10 patients with cirrhosis. We anticipate a 50% difference in these patients and the controls in the autophagy readouts and muscle biopsies will be performed	Other: Biopsies; Biopsy will be done on the Vastus Lateralis muscle in all groups
Steatohepatitis; This group will have 10 patients with alcoholic steatohepatitis that have more severe necroinflammation in the liver but for a shorter duration of illness and muscle biopsies will be performed	Other: Biopsies; Biopsy will be done on the Vastus Lateralis muscle in all groups
controls; This group will consist of 10 patients who are healthy and have no liver disease diagnosis and muscle biopsies will be performed	Other: Biopsies; Biopsy will be done on the Vastus Lateralis muscle in all groups

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Skeletal Muscle Autophagy	We will measure Malonyldialdehyde Acetaldehyde protein adducts to see skeletal muscle proteolysis during a one time muscle biopsy	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): May 18, 2015
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: April 14, 2017
• First Submitted That Met QC Criteria: July 3, 2017
• First Posted (Actual): July 6, 2017

Study Record Updates

• Last Update Posted (Estimated): January 9, 2026
• Last Update Submitted That Met QC Criteria: January 8, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Substance-Related Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Alcohol-Induced Disorders; Liver Diseases, Alcoholic; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Cytological Techniques; Cytodiagnosis; Diagnostic Techniques, Surgical; Biopsy
• Other Study ID Numbers: 14-1287

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
• product manufactured in and exported from the U.S.: No