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Recruiting NCT04740580

Glutathione, Brain Metabolism and Inflammation in Alzheimer's Disease

Early Phase I Interventional Alzheimer Disease

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Glycine, N-acetylcysteine, Alanine.
Who it may be relevant to
Registry conditions: Alzheimer Disease. Basic parameters: 55 years — 85 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Overview

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.

Interventions

  • Dietary supplement Glycine
    The active arm will supplement a combination of glycine and N-acetylcysteine (GlyNAC)
  • Dietary supplement N-acetylcysteine
    The active arm will supplement a combination of glycine and N-acetylcysteine (GlyNAC)
  • Dietary supplement Alanine
    The placebo arm will supplement Alanine

Primary outcome measures

  • Cognition [Time frame: Day 0 of supplementation, and 12-weeks and 24-weeks after starting supplementation]
  • Brain glucose uptake [Time frame: Done before supplementation and 24-weeks after starting supplementation]
  • Brain inflammation [Time frame: Done before supplementation and 24-weeks after starting supplementation]
Secondary outcome measures (9)
  • 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]

Eligibility criteria

Inclusion criteria

  • 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.

Exclusion criteria

  • 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;
  • 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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Triple blind
Primary purpose
Other

Study locations

United States · 1 center
  • Baylor College of Medicine — Houston

Identifiers

NCT: NCT04740580 · H48186

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗