Glutathione in Mild Cognitive Impairment

Elderly humans have an increased risk of dementia which begins as mild defects in memory called mild cognitive impairment. Glutathione (GSH), a key endogenous antioxidant has been linked to cognition. This exploratory study will investigate mechanisms linked to GSH for cognitive impairment (and improvement) by studying humans with mild cognitive impairment who will be evaluated 12-weeks after receiving either N-acetylcysteine and glycine (GSH precursors), or receiving alanine, and a further 12-weeks after stopping these supplements.

Study Overview

• Status: Active, not recruiting
• Conditions: Mild Cognitive Impairment
• Intervention / Treatment: Dietary supplement: Glycine; Dietary supplement: N-acetylcysteine (NAC); Dietary supplement: Alanine

Detailed Description

Subjects with MCI will be recruited by written informed consent using forms approved by the Baylor IRB. Subjects will stop nonvitamin supplements for 4wks before screening labs (blood count, HbA1c, glucose, lipid profile, liver profile, blood urea nitrogen, Creatinine, thyroid stimulating hormone, free T4), and for the entire 24wks duration of the study. 60 fasted subjects will have the following measures before and after 12wks of supplementation with cysteine (as N-acetylcysteine) plus glycine vs alanine: (1) Cognitive function using ADCS-PACC (Alzheimer's Disease Co-operative Study-Preclinical Alzheimer's Cognitive Composite which includes Free and Cued Selective Reminding Test, Immediate and Delayed paragraph recall score, Digit-Symbol Substitution Test, Mini mental state examination; (2) Red-cell concentrations of GSH, cysteine, glycine, glutamic acid; plasma malondialdehyde, F2/F3-isoprostanes, sICAM, sVCAM, E-selectin; endothelial function; (3) Mitochondrial glucose oxidation by calorimetry. Measures will be repeated for washout effects 12-wks after stopping supplements.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria at study entry: (1) Diagnosis of Mild Cognitive Impairment Exclusion Criteria at study entry: (1) hospitalization within past 3 months; (2) known diabetes; (3) creatinine greater than or equal to 1.5 mg/dL; (4) hemoglobin concentration less than 11 g/dL; (5) known liver disease, or AST/ALT greater than or equal to 2x ULN; (6) history of stroke, brain tumor, or active heart failure; (7) history of psychiatric disorders; (8) untreated depression.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: MCI-active; 30 Subjects with MCI will receive N-acetylcysteine and glycine for 12-weeks. ll subjects will be studied at baseline prior to supplementation, after completing 12-weeks of supplementation, and 12-weeks after stopping supplementation (i.e. at 24-weeks). Supplements are only provided for first 12-weeks.	Dietary supplement: Glycine; Dietary Supplement: glycine will be supplemented in the active arm for 12-weeks; Dietary supplement: N-acetylcysteine (NAC); Dietary Supplement: NAC will be supplemented in the active arm for 12-weeks
Placebo Comparator: MCI-placebo; 30 subjects will received alanine for 12-weeks. All subjects will be studied at baseline prior to supplementation, after completing 12-weeks of supplementation, and 12-weeks after stopping supplementation (i.e. at 24-weeks). Supplements are only provided for first 12-weeks	Dietary supplement: Alanine; Dietary Supplement: Alanine will be supplemented in the placebo arm for 12-weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognition	Measured using ADCS-PACC	Change between 0-weeks and 12-weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endothelial function markers sICAM, sVCAM, E-selectin	Measured in plasma	Change between 0-weeks and 12-weeks
Endothelial function	Measured using the EndoPAT system	Change between 0-weeks and 12-weeks
Mitochondrial fuel oxidation in fasted and fed states	Measured using calorimetry	Change between 0-weeks and 12-weeks
Concentrations of Glutathione	Measured in red cells	Change between 0-weeks and 12-weeks
Concentrations of TBARS, F2,F3 isoprostanes	Measured in plasma	Change between 0-weeks and 12-weeks
Insulin resistance	Measured as HOMA-IR	Change between 0-weeks and 12-weeks

Collaborators and Investigators

• Sponsor: Baylor College of Medicine
• Collaborators: The Methodist Hospital Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2018
• Primary Completion (Actual): May 30, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: February 22, 2018
• First Submitted That Met QC Criteria: April 3, 2018
• First Posted (Actual): April 10, 2018

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 20, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction; Amino Acids, Peptides, and Proteins; Sulfur Compounds; Organic Chemicals; Amino Acids; Cysteine; Amino Acids, Sulfur; Acetylcysteine; Glycine; Alanine
• Other Study ID Numbers: H42035: Glutathione in MCI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD will not be shared to anyone outside of investigating team

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No