Glutathione, Oxidative Stress and Mitochondrial Function in COVID-19

NCT ID: NCT04703036

Last Updated: 2024-06-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-11
• Study Completion Date: 2023-03-31

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.

Detailed Description

This study will investigate associated defects in the following two populations of patients with COVID-19:

Hospitalized patients admitted for COVID-19 will sign an informed consent form, and be randomized to receive either active (Glycine plus N-acetylcysteine) or a placebo (alanine) supplementation for 2-weeks. On day-0, the participants will have a single blood draw to measure measure oxidative stress, Glutathione levels, inflammatory cytokines, endothelial dysfunction, mitochondrial dysfunction, immune dysfunction, and complete questionnaires to assess fatigue, activity and cognition. Additional clinical and lab information will be obtained from the hospital electronic medical records. These measurements will be repeated 1-week and 2-weeks after starting supplementation, and at 4-weeks and 8-weeks after stopping supplementation.

Conditions

Covid19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: DOUBLE

Study Groups

Active arm

The active supplements are glycine and N-acetylcysteine

Group Type: EXPERIMENTAL

Glycine

Intervention Type: DIETARY_SUPPLEMENT

Glycine is an amino-acid (protein)

N-acetylcysteine

Intervention Type: DIETARY_SUPPLEMENT

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

Placebo arm

The placebo arm is alanine

Group Type: PLACEBO_COMPARATOR

Alanine

Intervention Type: DIETARY_SUPPLEMENT

Alanine is an amino-acid (protein)

Interventions

Glycine

Glycine is an amino-acid (protein)

Intervention Type: DIETARY_SUPPLEMENT

N-acetylcysteine

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

Intervention Type: DIETARY_SUPPLEMENT

Alanine

Alanine is an amino-acid (protein)

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• 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.

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Baylor College of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Rajagopal V Sekhar

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Baylor College of Medicine

Houston, Texas, United States

Countries

United States

Other Identifiers

H48057

Identifier Type: -

Identifier Source: org_study_id