Glutathione, Brain Metabolism and Inflammation in Alzheimer's Disease

NCT04740580 | Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: H48186
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

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.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (3)

• Cognition

  Measured using ADAS-Cog testing

  Day 0 of supplementation, and 12-weeks and 24-weeks after starting supplementation

• Brain glucose uptake

  Measured using brain FDG-PET scan

  Done before supplementation and 24-weeks after starting supplementation

• Brain inflammation

  Done using brain TSPO-PET scan

  Done before supplementation and 24-weeks after starting supplementation

Secondary Outcomes (9)

• Activities of daily living

  Day 0 of supplementation, 12-weeks and 24-weeks after starting supplementation

• Mitochondrial fuel oxidation

  Day 0 of supplementation, 12-weeks and 24-weeks after starting supplementation

• Red-blood cell glutathione, glycine, cysteine and glutamic aid

  Day 0 of supplementation, 12-weeks and 24-weeks after starting supplementation

• Oxidative stress

  Day 0 of supplementation, 12-weeks and 24-weeks after starting supplementation

• Damage due to oxidative stress

  Day 0 of supplementation, 12-weeks and 24-weeks after starting supplementation

Study Arms (2)

Glycine plus N-acetylcysteine

EXPERIMENTAL

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

Dietary Supplement: Glycine; Dietary Supplement: N-acetylcysteine

Alanine

PLACEBO COMPARATOR

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

Dietary Supplement: Alanine

Interventions

Glycine DIETARY_SUPPLEMENT

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

Glycine plus N-acetylcysteine

N-acetylcysteine DIETARY_SUPPLEMENT

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

Glycine plus N-acetylcysteine

Alanine DIETARY_SUPPLEMENT

The placebo arm will supplement Alanine

Alanine

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Baylor College of Medicine: lead
• The Methodist Hospital Research Institute: collaborator

Study Sites (1)

Baylor College of Medicine

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Glycine; Acetylcysteine; Alanine

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Amino Acids; Amino Acids, Peptides, and Proteins; Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals

Study Officials

• Rajagopal V Sekhar, M.D.

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rajagopal V Sekhar, M.D.

CONTACT

7137983908; rsekhar@bcm.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Placebo-controlled trial

Study Record Dates

• First Submitted: February 2, 2021
• First Posted: February 5, 2021
• Study Start: February 15, 2022
• Primary Completion: April 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: June 10, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)