Glutathione, Oxidative Stress and Mitochondrial Function in COVID-19

NCT04703036 | Terminated Early Phase 1 DMC

• 1 other identifier: H48057
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

COVID-19 is associated with increased mortality, and has been linked to a 'cytokine inflammatory storm'. Populations at higher risk of COVID complications and mortality include the elderly, diabetic patients and immunocompromised patients (such as HIV), and the investigators have studied these 3 populations over the past 20 years and have found that they all have deficiency of the endogenous antioxidant protein glutathione (GSH), elevated oxidative stress, inflammation, impaired mitochondrial function, immune dysfunction, and endothelial dysfunction. It is known and established that GSH adequacy is necessary for neutralizing harmful oxidative stress, and that elevated oxidative stress appears to promote mitochondrial dysfunction. The combination of oxidative stress and mitochondrial dysfunction have also been linked to inflammation, immune dysfunction, and endothelial dysfunction. In prior studies in aging, the investigators have also identified that supplementing glutathione precursor amino-acids glycine and cysteine (provided as N-acetylcysteine) improves GSH deficiency and mitochondrial function, and lowers oxidative stress, inflammation, and endothelial dysfunction. The investigators have coined the term GlyNAC to refer to the combination of glycine and N-acetylcysteine. This study will evaluate the prevalence and extent of these defects in patients with COVID-19 admitted to the hospital, and the response to supplementing GlyNAC or placebo for 2-weeks. Because patients with COVID-19 are also being reported to have fatigue and cognitive impairment, the investigators will also measure fatigue and cognition at admission, 1-week and 2-weeks after beginning supplementation. The supplementation is stopped after completing 2-weeks, and these outcomes will be measured again after 4-weeks and 8-weeks after stopping supplementation.

Conditions

Covid19

Outcome Measures

Primary Outcomes (3)

• Change in Glutathione concentrations

  Glutathione levels will be measured in red-blood cells

  Day 0, 3-days, 1-week, 2-weeks, 6-weeks, 10-weeks

• Change in Interleukein 6 concentrations

  Plasma IL-6 concentrations

  Day 0, 3-days, 1-week, 2-weeks, 6-weeks, 10-weeks

• Change in Ordinal scale

  This is a scale developed by the World-Health Organization for COVID trials. The clinical condition of each participant will be determined using this scale at 3 time points - Day 0, after 1-week and after-2weeks of supplementation

  Day 0, 1-week, 2-weeks

Secondary Outcomes (9)

• Change in oxidative stress

  Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks

• Change in marker of damage due to oxidative stress

  Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks

• Change in inflammatory cytokines

  Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks

• Change in mitochondrial energetics

  Day 0 1-week, 2-weeks, 6-weeks, 10-weeks

• Change in immune function

  Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks

Study Arms (2)

Active arm

EXPERIMENTAL

The active supplements are glycine and N-acetylcysteine

Dietary Supplement: Glycine; Dietary Supplement: N-acetylcysteine

Placebo arm

PLACEBO COMPARATOR

The placebo arm is alanine

Dietary Supplement: Alanine

Interventions

Glycine DIETARY_SUPPLEMENT

Glycine is an amino-acid (protein)

Active arm

N-acetylcysteine DIETARY_SUPPLEMENT

This is a donor of the amino-acid cysteine (protein)

Active arm

Alanine DIETARY_SUPPLEMENT

Alanine is an amino-acid (protein)

Placebo arm

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 55-85y;
• Diagnosis of COVID-19;
• Hospitalized patients.

You may not qualify if:

• Active heart disease or active cancer at time of recruitment;
• Patients in Intensive Care Unit at the time of recruitment;
• Patents with alanine transaminase and aspartate transaminase greater than 5 times the upper limit of normal at any time;
• Patients requiring \>4L per minute of oxygen support at the time of recruitment.

Sponsors & Collaborators

• Baylor College of Medicine: lead

Study Sites (1)

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

COVID-19

Interventions

Glycine; Acetylcysteine; Alanine

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Amino Acids; Amino Acids, Peptides, and Proteins; Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Participants and the investigative team are masked. Only the biostatistician will be unmasked to the identity of the active and placebo groups.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Randomized controlled trial, placebo-controlled, double-blind design

Study Record Dates

• First Submitted: January 6, 2021
• First Posted: January 11, 2021
• Study Start: January 11, 2021
• Primary Completion: March 31, 2023
• Study Completion: March 31, 2023
• Last Updated: June 26, 2024

Record last verified: 2024-06

Locations

US (1)