Glutathione in Mild Cognitive Impairment

• Sponsor: Baylor College of Medicine (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT03493178
• Collaborator: The Methodist Hospital Research Institute (Other)
• Enrollment: 60
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 68.6
• Patients Per Site Per Month: 0.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Mild Cognitive Impairment	Dietary Supplement: Glycine; Dietary Supplement: N-acetylcysteine (NAC); Dietary Supplement: Alanine	Early Phase 1

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Other
• Official Title: Glutathione in Mild Cognitive Impairment
• Actual Study Start Date: Apr 14, 2018
• Anticipated Primary Completion Date: May 31, 2023
• Anticipated Study Completion Date: Dec 31, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Cognition [Change between 0-weeks and 12-weeks]

   Measured using ADCS-PACC

Secondary Outcome Measures

1. Concentrations of Glutathione, cysteine, glycine, glutamic acid [Change between 0-weeks and 12-weeks]

   Measured in red cells

2. Concentrations of malondialdehyde, F2,F3 isoprostanes [Change between 0-weeks and 12-weeks]

   Measured in plasma

3. Endothelial function markers sICAM, sVCAM, E-selectin [Change between 0-weeks and 12-weeks]

   Measured in plasma

4. Endothelial function [Change between 0-weeks and 12-weeks]

   Measured using the EndoPAT system

5. Mitochondrial fuel oxidation in fasted and fed states [Change between 0-weeks and 12-weeks]

   Measured using calorimetry

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Baylor College of Medicine	Houston	Texas	United States	77030

Sponsors and Collaborators

• Baylor College of Medicine
• The Methodist Hospital Research Institute

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Rajagopal V Sekhar, Associate Professor of Medicine, Baylor College of Medicine
• ClinicalTrials.gov Identifier: NCT03493178
• Other Study ID Numbers: H42035: Glutathione in MCI
• First Posted: Apr 10, 2018
• Last Update Posted: Feb 11, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Additional relevant MeSH terms: Cognitive Dysfunction; Acetylcysteine; N-monoacetylcystine; Glycine

Study Results

No Results Posted as of Feb 11, 2022