Clinical trial NCT04703036: Glutathione, Oxidative Stress and Mitochondrial Function in COVID-19
Official title: Randomized Trial of Supplementing Glycine and N-acetylcysteine vs. Placebo in COVID-19
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: EARLY_PHASE1
Conditions: Covid19
Lead sponsor: Baylor College of Medicine
Sponsor class: OTHER
First posted: 2021-01-11
Enrollment: 4
Sex: ALL
Minimum age (years): 55
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized controlled trial, placebo-controlled, double-blind design
Primary purpose: OTHER

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.

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.

Primary outcomes:
measure: Change in Glutathione concentrations
timeFrame: Day 0, 3-days, 1-week, 2-weeks, 6-weeks, 10-weeks
measure: Change in Interleukein 6 concentrations
timeFrame: Day 0, 3-days, 1-week, 2-weeks, 6-weeks, 10-weeks
measure: Change in Ordinal scale
timeFrame: Day 0, 1-week, 2-weeks
Secondary outcomes:
measure: Change in oxidative stress
timeFrame: Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks
measure: Change in marker of damage due to oxidative stress
timeFrame: Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks
measure: Change in inflammatory cytokines
timeFrame: Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks
measure: Change in mitochondrial energetics
timeFrame: Day 0 1-week, 2-weeks, 6-weeks, 10-weeks
measure: Change in immune function
timeFrame: Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks
measure: Change in cognition
timeFrame: Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks
measure: Change in function
timeFrame: Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks
measure: Change in fatigue
timeFrame: Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks
measure: Change in circulating marker of memory
timeFrame: Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks
Other outcomes:
Locations:
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
Study officials:
References: