Ethanol Induces Skeletal Muscle Autophagy

Recruiting

• Conditions: Alcoholic Liver Disease
• Interventions: Other: Biopsies

• Registration Number: NCT03209791
• Lead Sponsor: The Cleveland Clinic

Brief Summary

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

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 Timeline

• Study Start: 2015-05-18
• Study First Submitted: 2017-04-14
• Study First Submitted QC: 2017-07-03
• Study First Posted: 2017-07-06
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-12
• Last Update Posted: 2025-03-13
• Primary Completion: 2026-06-30
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Cirrhosis	Biopsies	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
Steatohepatitis	Biopsies	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
Alcoholic Steatosis	Biopsies	This group will have 10 patients with alcoholic steatosis which is milder disease and muscle biopsies will be performed
controls	Biopsies	This group will consist of 10 patients who are healthy and have no liver disease diagnosis and muscle biopsies will be performed

Primary Outcome Measures

Name	Time	Method
Skeletal Muscle Autophagy	4 hours	We will measure Malonyldialdehyde Acetaldehyde protein adducts to see skeletal muscle proteolysis during a one time muscle biopsy

Trial Locations

Locations (1)

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States