Glutathione in Mild Cognitive Impairment

NCT ID: NCT03493178

Last Updated: 2025-08-24

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-19
• Study Completion Date: 2025-12-31

Brief Summary

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.

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.

Conditions

Mild Cognitive Impairment

Study Design

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

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Glycine

Intervention Type: DIETARY_SUPPLEMENT

Dietary Supplement: glycine will be supplemented in the active arm for 12-weeks

N-acetylcysteine (NAC)

Intervention Type: DIETARY_SUPPLEMENT

Dietary Supplement: NAC will be supplemented in the active arm for 12-weeks

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

Group Type: PLACEBO_COMPARATOR

Alanine

Intervention Type: DIETARY_SUPPLEMENT

Dietary Supplement: Alanine will be supplemented in the placebo arm for 12-weeks

Interventions

Glycine

Dietary Supplement: glycine will be supplemented in the active arm for 12-weeks

Intervention Type: DIETARY_SUPPLEMENT

N-acetylcysteine (NAC)

Dietary Supplement: NAC will be supplemented in the active arm for 12-weeks

Intervention Type: DIETARY_SUPPLEMENT

Alanine

Dietary Supplement: Alanine will be supplemented in the placebo arm for 12-weeks

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

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.

• 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 of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Baylor College of Medicine

Houston, Texas, United States

Countries

United States

Other Identifiers

H42035: Glutathione in MCI

Identifier Type: -

Identifier Source: org_study_id