Study of HMB-enriched Amino Acid Supplementation in Patients With Alcoholic Liver Disease and COVID-19

Evaluate the Molecular Mechanisms of HMB-enriched Amino Acid Supplement to Reverse Muscle Loss in Patients With Alcoholic Liver Disease and COVID-19

Patients with COVID-19 and comorbidities including alcohol associated liver disease (ALD) are at risk for severe illness and abrupt or sudden clinical deterioration with ventilatory failure. â-hydroxy â-methyl butyrate (HMB), a non-nitrogenous leucine metabolite with anabolic properties, increases muscle mass and contractile function and enhances immune function. We aim to study the natural course of COVID-19 in patients with ALD and test whether HMB can affect ventilatory deterioration and improve short and long-term morbidity, mortality, and recovery from critical illness in symptomatic COVID-19 patients with ALD.

Study Overview

• Status: Recruiting
• Conditions: Alcoholic Liver Disease; COVID 19 Pneumonia
• Intervention / Treatment: Dietary supplement: β-hydroxy β-methyl butyrate (HMB) enriched amino acid; Dietary supplement: Balanced amino acid

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Alina Tuladhar, MPH; Phone Number: 216-445-6268; Email: tuladha@ccf.org
• Study Contact Backup: Name: Annette Bellar, MSLA; Phone Number: 216-445-0688; Email: bellara@ccf.org

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic Foundation
      • Contact: Alina Tuladhar, MPH; Phone Number: 216-445-6268; Email: tuladha@ccf.org
      • Principal Investigator: Srinivasan Dasarathy, MD
      • Contact: Annette Bellar, MSLA; Phone Number: 216-445-0688; Email: bellara@ccf.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

A. Cases: Patients with ALD and COVID-19 pneumonia:

1. Clinical, imaging, laboratory, and/or histological diagnosis of alcoholic cirrhosis and/or alcoholic hepatitis
2. Child Pugh score 5-8, serum creatinine <3, Model for End Stage Liver Disease score (MELD) <25
3. Diagnosis of COVID-19 pneumonia as defined by the WHO criteria: confirmed SARS-CoV-2 infection by PCR, evidence of bilateral pulmonary infiltrates on chest radiograph (CXR) or computed tomography (CT) and SpO2 <93% or on oxygen supplement
4. Age of 21 years or older

B. Controls: Patients without alcoholic liver disease (Non-ALD) and COVID-19 pneumonia:

1. Diagnosis of COVID-19 pneumonia as defined by the WHO criteria: confirmed SARS-CoV-2 infection by PCR, evidence of bilateral pulmonary infiltrates on chest radiograph (CXR) or computed tomography (CT) and SpO2 <93% or on oxygen supplement
2. Age of 21 years or older

Exclusion Criteria: (Both Cases and Controls)

1. Patients requiring active ventilator support
2. Anticoagulant/antiplatelet therapy (for those in the biopsy arm, see Randomization schema. If clinically feasible, patients will be asked to hold their anticoagulants for the muscle biopsy after physician review),
3. Recent gastrointestinal bleeding (<3 months)
4. Advanced organ diseases: congestive heart failure (NYHA class 3 and 4), chronic obstructive pulmonary diseases (COPD) (GOLD stage 3 and 4), chronic kidney disease (Cr>3), metastatic malignancy
5. Medications that alter muscle protein metabolism except systemic corticosteroids
6. Pregnancy
7. Unwillingness/ Inability to sign informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: HMB enriched amino acid arm; The patients randomized to the HMB enriched amino acid (HMB/EAA) arm will be given HMB/EAA for 90 days.	Dietary supplement: β-hydroxy β-methyl butyrate (HMB) enriched amino acid; β-hydroxy β-methyl butyrate (HMB) is a non-nitrogenous leucine metabolite with anabolic properties.
Placebo Comparator: Balanced amino acid arm; The patients randomized to the Balanced amino acid (BAA) arm will be given BAA for 90 days.	Dietary supplement: Balanced amino acid; Balanced amino acid is the balanced mixture of the various essential amino acids.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in skeletal muscle mass at Day 0 and Day 90	Baseline and Day 90
Number of hospital admissions between Day 0 and Day 90	Baseline and Day 90

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2021
• Primary Completion (Estimated): March 31, 2025
• Study Completion (Estimated): March 31, 2025

Study Registration Dates

• First Submitted: April 21, 2021
• First Submitted That Met QC Criteria: April 21, 2021
• First Posted (Actual): April 26, 2021

Study Record Updates

• Last Update Posted (Estimated): January 8, 2024
• Last Update Submitted That Met QC Criteria: January 4, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Digestive System Diseases; Alcohol-Related Disorders; Substance-Related Disorders; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Alcohol-Induced Disorders; Liver Diseases; COVID-19; Liver Diseases, Alcoholic
• Other Study ID Numbers: 20-1194

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