Glutathione, Oxidative Stress and Mitochondrial Function in COVID-19

Covid19 Clinical Trial

Official title:

Randomized Trial of Supplementing Glycine and N-acetylcysteine vs. Placebo in COVID-19

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04703036
• Other study ID #: H48057
• Status: Active, not recruiting
• Phase: Early Phase 1
• Start date: January 11, 2021
• Est. completion date: December 31, 2023

Study information

• Verified date: May 2023
• Source: Baylor College of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 64
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19
• Covid19

Intervention

Dietary Supplement:
• Glycine
Glycine is an amino-acid (protein)
• N-acetylcysteine
This is a donor of the amino-acid cysteine (protein)
• Alanine
Alanine is an amino-acid (protein)

Locations

Country	Name	City	State
United States	Baylor College of Medicine	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Baylor College of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Change in Interleukein 6 concentrations	Plasma IL-6 concentrations	Day 0, 3-days, 1-week, 2-weeks, 6-weeks, 10-weeks
Primary	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	Change in oxidative stress	Plasma concentrations of TBARS	Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks
Secondary	Change in marker of damage due to oxidative stress	Plasma concentrations of F2-isoprostanes	Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks
Secondary	Change in inflammatory cytokines	Plasma concentrations of TNFa, hsCRP, IL-10, PAI-1, D-dimer	Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks
Secondary	Change in mitochondrial energetics	Energetics measured by high-resolution respirometry in peripheral blood monocytes	Day 0 1-week, 2-weeks, 6-weeks, 10-weeks
Secondary	Change in immune function	The trial will evaluate if COVID-related disease severity is associated with NK cell deficiency and antigen presenting cell production of IL-6 and TNF.	Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks
Secondary	Change in cognition	Measured using Montreal cognitive assessment which ranges from 0-30	Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks
Secondary	Change in function	Measured using the Katz-activities of daily living	Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks
Secondary	Change in fatigue	Measured using the Facit-F fatigue scale	Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks
Secondary	Change in circulating marker of memory	Plasma BDNF concentrations	Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks