Alzheimer DiseaseEarly Phase 1NCT04740580
Glutathione, Brain Metabolism and Inflammation in Alzheimer's Disease
A Early Phase 1 study testing Glycine, N-acetylcysteine and Alanine in people with Alzheimer Disease, run by Baylor College of Medicine at 1 site in United States.
Trial summary
Alzheimer's disease (AD) is associated with significant, progressive cognitive decline. Key defects in mitochondrial fuel metabolism insulin resistance, inflammation and decreased brain glucose uptake are linked to AD. This trial will investigate the effects of supplementing glycine and N-acetylcysteine vs. Read more about this study
- Who is it for?
- Ages 55 to 85 years
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- Glycine, N-acetylcysteine and Alanine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 52 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Feb 2022to 31 Dec 2027
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
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 55-85 years;
- Gradual and progressive memory loss for more than 1 year, with a Montreal Cognitive Assessment score of 10-20;
- Amyloid positivity on PET scan;
- Availability of a study partner.
Who cannot join
- hospitalization in past 3 months;
- use of insulin medications;
- untreated thyroid disease;
- creatinine levels >1.5 mg/dL;
- hemoglobin concentration <11.0 g/dL;
- known liver disease, or AST/ALT level >2x ULN;
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- history of stroke, brain tumor, active heart failure or active cancer (removable basal cell cancers will not be an exclusion criteria);
- untreated depression or other severe psychiatric disorders;
- pregnancy or nursing (unlikely in this population)
Trial locations and contacts
1 site in 1 country.
About this study
Alzheimer's disease (AD) is associated with significant, progressive cognitive decline. Key defects in mitochondrial fuel metabolism insulin resistance, inflammation and decreased brain glucose uptake are linked to AD. This trial will investigate the effects of supplementing glycine and N-acetylcysteine vs. alanine as placebo on these defects in AD, and examine the effects on cognition.
Read the detailed description
Glutathione (GSH) deficiency, oxidative stress, mitochondrial dysfunction, insulin resistance and inflammation are linked to Alzheimer's disease (AD). In prior studies, investigators have shown that GSH deficiency contributes to mitochondrial impairment and oxidative stress, and that GSH deficiency can be corrected by supplementing its precursors glycine and cysteine (provided as N-acetylcysteine, NAC), with the combination termed GlyNAC.
This randomized clinical trial will evaluate the effect of GlyNAC vs. alanine placebo supplementation provided for 24-weeks to patients with AD, and measure changes in cognition, GSH concentrations, oxidative stress, brain glucose uptake, brain inflammation and insulin resistance.
Participants who are positive for a beta-amyloid PET scan and meeting cognitive screening criteria will be recruited, and enrolled only after meeting eligibility criteria. Before beginning study supplementation they will undergo imaging studies (MRI, FDG-PET and TSPO-PET scans), and only the FDG- and TSPO-PET scans will be repeated after completing 24-weeks of nutrient supplementation. Cognitive measurements, metabolic and mitochondrial measurements (as described below) will be done before supplementation, and after 12-weeks and 24-weeks of completing supplementation.
- Conditions
- Alzheimer Disease
- Being tested
- Glycine, N-acetylcysteine, Alanine
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GlycineDietary supplement
The active arm will supplement a combination of glycine and N-acetylcysteine (GlyNAC)
N-acetylcysteineDietary supplement
The active arm will supplement a combination of glycine and N-acetylcysteine (GlyNAC)
AlanineDietary supplement
The placebo arm will supplement Alanine
| Study group | Role | What they receive |
|---|---|---|
| Glycine plus N-acetylcysteine | Experimental | Glycine and cysteine are amino-acid (protein) precursors of glutathione. Cysteine is provided as N-acetylcysteine Receives: Dietary Supplement: Glycine; Dietary Supplement: N-acetylcysteine |
| Alanine | Placebo comparator | Alanine is an amino-acid (protein), and not a precursor of glutathione synthesis Receives: Dietary Supplement: Alanine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cognition
Measured using ADAS-Cog testing
Measured: Day 0 of supplementation, and 12-weeks and 24-weeks after starting supplementation
Brain glucose uptake
Measured using brain FDG-PET scan
Measured: Done before supplementation and 24-weeks after starting supplementation
Brain inflammation
Done using brain TSPO-PET scan
Measured: Done before supplementation and 24-weeks after starting supplementation
Secondary outcomes (9)
Activities of daily living
Measured using the ADCS-ADL scale
Measured: Day 0 of supplementation, 12-weeks and 24-weeks after starting supplementation
Mitochondrial fuel oxidation
Measured using indirect calorimetry in the fasted and post-glucose fed state
Measured: Day 0 of supplementation, 12-weeks and 24-weeks after starting supplementation
Red-blood cell glutathione, glycine, cysteine and glutamic aid
Measured using UPLC
Measured: Day 0 of supplementation, 12-weeks and 24-weeks after starting supplementation
Oxidative stress
Measured as plasma concentrations of TBARS and malondialdehyde
Measured: Day 0 of supplementation, 12-weeks and 24-weeks after starting supplementation
Damage due to oxidative stress
Measured as plasma concentration of isoprostanes
Measured: Day 0 of supplementation, 12-weeks and 24-weeks after starting supplementation
Inflammatory cytokines
Measured as plasma concentrations of IL6, TNFa
Measured: Day 0 of supplementation, 12-weeks and 24-weeks after starting supplementation
Endothelial dysfunction
Measured as plasma concentrations of sICAM1, sVCAM1, E-selectin
Measured: Day 0 of supplementation, 12-weeks and 24-weeks after starting supplementation
Plasma concentration of Brain-derived neurotropic factor (BDNF)
Measured using an ELISA kit
Measured: Day 0 of supplementation, 12-weeks and 24-weeks after starting supplementation
Mitochondrial energetics
Measured using the Oroboros high-resolution respirometer
Measured: Day 0 of supplementation, 12-weeks and 24-weeks after starting supplementation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2021
- Study start15 Feb 2022
- Primary completion30 Aug 2026
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer DiseaseStudies 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
- Placebo-controlled trial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 52 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- The Methodist Hospital Research Institute
- Responsible party
- Principal investigator, Rajagopal V Sekhar, Baylor College of Medicine
- Investigators
- Rajagopal V Sekhar, M.D., Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04740580
- Sponsor's protocol ID
- H48186
- Status last verified
- Sep 2026
- First submitted
- 2 Feb 2021
- Last updated
- 9 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Glutathione, Brain Metabolism and Inflammation in Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT04740580
- Acronym / sponsor ID
- H48186
- Conditions
- Alzheimer Disease
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 52 participants (estimated)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Collaborators
- The Methodist Hospital Research Institute
- Study start
- 15 Feb 2022 (actual)
- Primary completion
- 30 Aug 2026 (actual)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 5 Feb 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.
Alzheimer's disease (AD) is associated with significant, progressive cognitive decline. Key defects in mitochondrial fuel metabolism insulin resistance, inflammation and decreased brain glucose uptake are linked to AD. This trial will investigate the effects of supplementing glycine and N-acetylcysteine vs. alanine as placebo on these defects in AD, and examine the effects on cognition.
Detailed description
Glutathione (GSH) deficiency, oxidative stress, mitochondrial dysfunction, insulin resistance and inflammation are linked to Alzheimer's disease (AD). In prior studies, investigators have shown that GSH deficiency contributes to mitochondrial impairment and oxidative stress, and that GSH deficiency can be corrected by supplementing its precursors glycine and cysteine (provided as N-acetylcysteine, NAC), with the combination termed GlyNAC.
This randomized clinical trial will evaluate the effect of GlyNAC vs. alanine placebo supplementation provided for 24-weeks to patients with AD, and measure changes in cognition, GSH concentrations, oxidative stress, brain glucose uptake, brain inflammation and insulin resistance.
Participants who are positive for a beta-amyloid PET scan and meeting cognitive screening criteria will be recruited, and enrolled only after meeting eligibility criteria. Before beginning study supplementation they will undergo imaging studies (MRI, FDG-PET and TSPO-PET scans), and only the FDG- and TSPO-PET scans will be repeated after completing 24-weeks of nutrient supplementation. Cognitive measurements, metabolic and mitochondrial measurements (as described below) will be done before supplementation, and after 12-weeks and 24-weeks of completing supplementation.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Placebo-controlled trial
| Arm | Type | Receives |
|---|---|---|
| Glycine plus N-acetylcysteine | Experimental | Dietary Supplement: Glycine, Dietary Supplement: N-acetylcysteineGlycine and cysteine are amino-acid (protein) precursors of glutathione. Cysteine is provided as N-acetylcysteine |
| Alanine | Placebo comparator | Dietary Supplement: AlanineAlanine is an amino-acid (protein), and not a precursor of glutathione synthesis |
Who may qualify
- Ages
- 55 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age 55-85 years;
- Gradual and progressive memory loss for more than 1 year, with a Montreal Cognitive Assessment score of 10-20;
- Amyloid positivity on PET scan;
- Availability of a study partner.
Key exclusion criteria (9 listed)
- hospitalization in past 3 months;
- use of insulin medications;
- untreated thyroid disease;
- creatinine levels >1.5 mg/dL;
- hemoglobin concentration <11.0 g/dL;
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 |
|---|---|---|
| GlycineThe active arm will supplement a combination of glycine and N-acetylcysteine (GlyNAC) | Dietary supplement | Glycine plus N-acetylcysteine |
| N-acetylcysteineThe active arm will supplement a combination of glycine and N-acetylcysteine (GlyNAC) | Dietary supplement | Glycine plus N-acetylcysteine |
| AlanineThe placebo arm will supplement Alanine | Dietary supplement | Alanine |
Primary outcome
Cognition
Time frame: Day 0 of supplementation, and 12-weeks and 24-weeks after starting supplementation
Measured using ADAS-Cog testing
Brain glucose uptake
Time frame: Done before supplementation and 24-weeks after starting supplementation
Measured using brain FDG-PET scan
Brain inflammation
Time frame: Done before supplementation and 24-weeks after starting supplementation
Done using brain TSPO-PET scan
9 secondary outcomes
Activities of daily living
Time frame: Day 0 of supplementation, 12-weeks and 24-weeks after starting supplementation
Mitochondrial fuel oxidation
Time frame: Day 0 of supplementation, 12-weeks and 24-weeks after starting supplementation
Red-blood cell glutathione, glycine, cysteine and glutamic aid
Time frame: Day 0 of supplementation, 12-weeks and 24-weeks after starting supplementation
Oxidative stress
Time frame: Day 0 of supplementation, 12-weeks and 24-weeks after starting supplementation
Damage due to oxidative stress
Time frame: Day 0 of supplementation, 12-weeks and 24-weeks after starting supplementation
Inflammatory cytokines
Time frame: Day 0 of supplementation, 12-weeks and 24-weeks after starting supplementation
Endothelial dysfunction
Time frame: Day 0 of supplementation, 12-weeks and 24-weeks after starting supplementation
Plasma concentration of Brain-derived neurotropic factor (BDNF)
Time frame: Day 0 of supplementation, 12-weeks and 24-weeks after starting supplementation
Mitochondrial energetics
Time frame: Day 0 of supplementation, 12-weeks and 24-weeks after starting supplementation
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2026.
- Individual participant dataSharing planned: No
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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.
Rajagopal V Sekhar, M.D. principal investigator
Baylor College of Medicine
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 Alzheimer Disease, 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 4 inclusion and 9 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: under way, not looking for participants, as of the sponsor's last update on 9 Sep 2026. 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?
This study is still under way. Results are not available in the source record yet.
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?
Cognition (time frame: Day 0 of supplementation, and 12-weeks and 24-weeks after starting supplementation). 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 9 Sep 2026.