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Glutathione in Mild Cognitive Impairment

Early Phase 1
Active, not recruiting
Conditions
Mild Cognitive Impairment
Interventions
Dietary Supplement: Alanine
Dietary Supplement: Glycine
Dietary Supplement: N-acetylcysteine (NAC)
Registration Number
NCT03493178
Lead Sponsor
Baylor College of Medicine
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.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
60
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
MCI-activeN-acetylcysteine (NAC)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.
MCI-placeboAlanine30 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
MCI-activeGlycine30 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.
Primary Outcome Measures
NameTimeMethod
CognitionChange between 0-weeks and 12-weeks

Measured using ADCS-PACC

Secondary Outcome Measures
NameTimeMethod
Mitochondrial fuel oxidation in fasted and fed statesChange between 0-weeks and 12-weeks

Measured using calorimetry

Endothelial function markers sICAM, sVCAM, E-selectinChange between 0-weeks and 12-weeks

Measured in plasma

Endothelial functionChange between 0-weeks and 12-weeks

Measured using the EndoPAT system

Concentrations of Glutathione, cysteine, glycine, glutamic acidChange between 0-weeks and 12-weeks

Measured in red cells

Concentrations of malondialdehyde, F2,F3 isoprostanesChange between 0-weeks and 12-weeks

Measured in plasma

Trial Locations

Locations (1)

Baylor College of Medicine

🇺🇸

Houston, Texas, United States

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