Covid19Early Phase 1NCT04703036
Glutathione, Oxidative Stress and Mitochondrial Function in COVID-19
A Early Phase 1 study testing Glycine, N-acetylcysteine and Alanine in people with Covid19, run by Baylor College of Medicine at 1 site in United States.
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… Read more about this study
- Who is it for?
- Ages 55 to 85 years
- Conditions the study is for
- Covid19
- What is being tested?
- Glycine, N-acetylcysteine and Alanine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Jan 2021to 31 Mar 2023
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 55-85y;
- Diagnosis of COVID-19;
- Hospitalized patients.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized Trial of Supplementing Glycine and N-acetylcysteine vs. Placebo in COVID-19
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.
Read the 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
- Being tested
- Glycine, N-acetylcysteine, Alanine
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GlycineDietary supplement
Glycine is an amino-acid (protein)
N-acetylcysteineDietary supplement
This is a donor of the amino-acid cysteine (protein)
AlanineDietary supplement
Alanine is an amino-acid (protein)
| Study group | Role | What they receive |
|---|---|---|
| Active arm | Experimental | The active supplements are glycine and N-acetylcysteine Receives: Dietary Supplement: Glycine; Dietary Supplement: N-acetylcysteine |
| Placebo arm | Placebo comparator | The placebo arm is alanine Receives: Dietary Supplement: Alanine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Glutathione concentrations
Glutathione levels will be measured in red-blood cells
Measured: Day 0, 3-days, 1-week, 2-weeks, 6-weeks, 10-weeks
Change in Interleukein 6 concentrations
Plasma IL-6 concentrations
Measured: 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
Measured: Day 0, 1-week, 2-weeks
Secondary outcomes (9)
Change in oxidative stress
Plasma concentrations of TBARS
Measured: Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks
Change in marker of damage due to oxidative stress
Plasma concentrations of F2-isoprostanes
Measured: Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks
Change in inflammatory cytokines
Plasma concentrations of TNFa, hsCRP, IL-10, PAI-1, D-dimer
Measured: Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks
Change in mitochondrial energetics
Energetics measured by high-resolution respirometry in peripheral blood monocytes
Measured: Day 0 1-week, 2-weeks, 6-weeks, 10-weeks
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.
Measured: Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks
Change in cognition
Measured using Montreal cognitive assessment which ranges from 0-30
Measured: Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks
Change in function
Measured using the Katz-activities of daily living
Measured: Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks
Change in fatigue
Measured using the Facit-F fatigue scale
Measured: Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks
Change in circulating marker of memory
Plasma BDNF concentrations
Measured: Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2021
- Study start11 Jan 2021
- Primary completion31 Mar 2023
- Study completion31 Mar 2023
Why it stopped: Futility due to inability to recruit participants meeting entry criteria.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Covid19Studies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized controlled trial, placebo-controlled, double-blind design
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rajagopal V Sekhar, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04703036
- Sponsor's protocol ID
- H48057
- Status last verified
- Jun 2024
- First submitted
- 6 Jan 2021
- Last updated
- 26 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Trial of Supplementing Glycine and N-acetylcysteine vs. Placebo in COVID-19
- ClinicalTrials.gov ID
- NCT04703036
- Acronym / sponsor ID
- H48057
- Conditions
- Covid19
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Futility due to inability to recruit participants meeting entry criteria.
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Study start
- 11 Jan 2021 (actual)
- Primary completion
- 31 Mar 2023 (actual)
- Study completion
- 31 Mar 2023 (actual)
- First posted
- 11 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Randomized controlled trial, placebo-controlled, double-blind design
| Arm | Type | Receives |
|---|---|---|
| Active arm | Experimental | Dietary Supplement: Glycine, Dietary Supplement: N-acetylcysteineThe active supplements are glycine and N-acetylcysteine |
| Placebo arm | Placebo comparator | Dietary Supplement: AlanineThe placebo arm is alanine |
Who may qualify
- Ages
- 55 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age 55-85y;
- Diagnosis of COVID-19;
- Hospitalized patients.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GlycineGlycine is an amino-acid (protein) | Dietary supplement | Active arm |
| N-acetylcysteineThis is a donor of the amino-acid cysteine (protein) | Dietary supplement | Active arm |
| AlanineAlanine is an amino-acid (protein) | Dietary supplement | Placebo arm |
Primary outcome
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 Interleukein 6 concentrations
Time frame: Day 0, 3-days, 1-week, 2-weeks, 6-weeks, 10-weeks
Plasma IL-6 concentrations
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
9 secondary outcomes
Change in oxidative stress
Time frame: Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks
Change in marker of damage due to oxidative stress
Time frame: Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks
Change in inflammatory cytokines
Time frame: Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks
Change in mitochondrial energetics
Time frame: Day 0 1-week, 2-weeks, 6-weeks, 10-weeks
Change in immune function
Time frame: Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks
Change in cognition
Time frame: Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks
Change in function
Time frame: Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks
Change in fatigue
Time frame: Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks
Change in circulating marker of memory
Time frame: Day 0, 1-week, 2-weeks, 6-weeks, 10-weeks
Results and safety
The study was stopped early (reason given: Futility due to inability to recruit participants meeting entry criteria.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2024.
Related trials for Covid19
Recruiting
Whole-body Cryotherapy in Those With Chronic Fatigue: A Feasibility Study
ME/CFS, Fibromyalgia (FM)
Not yet recruitingPhase 1
Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)
Post-Acute COVID-19 Syndrome
Active, not recruiting
Working Towards Empowered Community-driven Approaches to Increase Vaccination and Preventive Care Engagement
COVID-19
Active, not recruitingObservational study
Epigenetic Changes in Long COVID Patients
Long COVID-19 Syndrome, Long COVID Symptoms
RecruitingPhase 3
Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia
Respiratory Tract Diseases, Influenza (Pandemic)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Glycine, N-acetylcysteine and Alanine in people with Covid19, run by Baylor College of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Futility due to inability to recruit participants meeting entry criteria.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Glutathione concentrations (time frame: Day 0, 3-days, 1-week, 2-weeks, 6-weeks, 10-weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2024.