Glutathione in Mild Cognitive Impairment
Overview
- Phase
- Early Phase 1
- Intervention
- Not specified
- Conditions
- Mild Cognitive Impairment
- Sponsor
- Baylor College of Medicine
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Cognition
- Status
- Active, not recruiting
- Last Updated
- last month
Overview
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.
Investigators
Rajagopal V Sekhar
Associate Professor of Medicine
Baylor College of Medicine
Eligibility 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.
Outcomes
Primary Outcomes
Cognition
Time Frame: Change between 0-weeks and 12-weeks
Measured using ADCS-PACC
Secondary Outcomes
- Concentrations of Glutathione(Change between 0-weeks and 12-weeks)
- Concentrations of TBARS, F2,F3 isoprostanes(Change between 0-weeks and 12-weeks)
- Endothelial function markers sICAM, sVCAM, E-selectin(Change between 0-weeks and 12-weeks)
- Endothelial function(Change between 0-weeks and 12-weeks)
- Mitochondrial fuel oxidation in fasted and fed states(Change between 0-weeks and 12-weeks)
- Insulin resistance(Change between 0-weeks and 12-weeks)