Randomized Trial of Supplementing Glycine and N-acetylcysteine vs. Placebo in COVID-19
Trial Snapshot
- Phase
- Early Phase 1
- Status
- Terminated
- Sponsor
- Baylor College of Medicine
- Enrollment
- 4
- Locations
- 2
- Primary Endpoint
- Change in Glutathione concentrations
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Other
- Masking
- Double (Participant, Investigator)
Masking Description
Participants and the investigative team are masked. Only the biostatistician will be unmasked to the identity of the active and placebo groups.
Eligibility Criteria
- Ages
- 55 Years to 85 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Outcomes
Primary Outcomes
Change in Glutathione concentrations
Time Frame: Day 0, 3-days, 1-week, 2-weeks, 6-weeks, 10-weeks
Glutathione levels will be measured in red-blood cells
Change in Ordinal scale
Time Frame: Day 0, 1-week, 2-weeks
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
Change in Interleukein 6 concentrations
Time Frame: Day 0, 3-days, 1-week, 2-weeks, 6-weeks, 10-weeks
Plasma IL-6 concentrations
Secondary Outcomes
- Change in inflammatory cytokines(Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks)
- Change in circulating marker of memory(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 oxidative stress(Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks)
- Change in function(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 cognition(Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks)
- Change in fatigue(Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks)
- Change in immune function(Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks)
Investigators
Rajagopal V Sekhar
Principal Investigator
Baylor College of Medicine