Glutathione, Brain Metabolism and Inflammation in Alzheimer's Disease

Baylor College of Medicine

Status and phase: Enrolling; Early Phase 1

Conditions: Alzheimer Disease

Treatments: Dietary Supplement: Glycine; Dietary Supplement: Alanine; Dietary Supplement: N-acetylcysteine

Study type: Interventional

Funder types: Other

Identifiers

NCT04740580

H48186

Details and patient eligibility

About

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.

Full 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.

Enrollment: 52 estimated patients

Sex: All

Ages: 55 to 85 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

---

52 participants in 2 patient groups, including a placebo group

Glycine plus N-acetylcysteine

Experimental group

Description:

Glycine and cysteine are amino-acid (protein) precursors of glutathione. Cysteine is provided as N-acetylcysteine

Treatment:

Dietary Supplement: N-acetylcysteine

Dietary Supplement: Glycine

Alanine

Placebo Comparator group

Description:

Alanine is an amino-acid (protein), and not a precursor of glutathione synthesis

Treatment:

Dietary Supplement: Alanine