Glutathione, Brain Metabolism and Inflammation in Alzheimer's Disease

NCT ID: NCT04740580

Last Updated: 2025-06-10

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-15
• Study Completion Date: 2026-12-31

Brief 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. 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.

Conditions

Alzheimer Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: TRIPLE

Study Groups

Glycine plus N-acetylcysteine

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

Group Type: EXPERIMENTAL

Glycine

Intervention Type: DIETARY_SUPPLEMENT

The active arm will supplement a combination of glycine and N-acetylcysteine (GlyNAC)

N-acetylcysteine

Intervention Type: DIETARY_SUPPLEMENT

The active arm will supplement a combination of glycine and N-acetylcysteine (GlyNAC)

Alanine

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

Group Type: PLACEBO_COMPARATOR

Alanine

Intervention Type: DIETARY_SUPPLEMENT

The placebo arm will supplement Alanine

Interventions

Glycine

The active arm will supplement a combination of glycine and N-acetylcysteine (GlyNAC)

Intervention Type: DIETARY_SUPPLEMENT

N-acetylcysteine

The active arm will supplement a combination of glycine and N-acetylcysteine (GlyNAC)

Intervention Type: DIETARY_SUPPLEMENT

Alanine

The placebo arm will supplement Alanine

Intervention Type: DIETARY_SUPPLEMENT

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;
• untreated depression or other severe psychiatric disorders;
• pregnancy or nursing (unlikely in this population)

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Methodist Hospital Research Institute

OTHER

Sponsor Role: collaborator

Baylor College of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Rajagopal V Sekhar

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rajagopal V Sekhar, M.D.

Role: PRINCIPAL_INVESTIGATOR

Baylor College of Medicine

Locations

Baylor College of Medicine

Houston, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Rajagopal V Sekhar, M.D.

Role: CONTACT

rsekhar@bcm.edu

7137983908

Facility Contacts

Rajagopal V Sekhar, MD

Role: primary

rsekhar@bcm.edu

713-798-3908

Other Identifiers

H48186

Identifier Type: -

Identifier Source: org_study_id