Ethanol Induces Skeletal Muscle Autophagy

Sponsor

The Cleveland Clinic (Other)

Overall Status

Recruiting

CT.gov ID

NCT03209791

Collaborator

(none)

Enrollment

Location

103.5

Anticipated Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Alcoholic Liver Disease	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 Design

Study Type:

Observational

Anticipated Enrollment :

40 participants

Observational Model:

Case-Control

Time Perspective:

Cross-Sectional

Official Title:

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

Actual Study Start Date :

May 18, 2015

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	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

Outcome Measures

Primary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cleveland Clinic	Cleveland	Ohio	United States	44195

Sponsors and Collaborators

The Cleveland Clinic

Investigators

Principal Investigator: Srinivasan Dasarathy, MD, The Cleveland Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Srinivasan Dasarathy, Staff Physician, The Cleveland Clinic

ClinicalTrials.gov Identifier:

NCT03209791

Other Study ID Numbers:

14-1287

First Posted:

Jul 6, 2017

Last Update Posted:

Aug 20, 2021

Last Verified:

Aug 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Liver Diseases

Liver Diseases, Alcoholic

Study Results

No Results Posted as of Aug 20, 2021