- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01870193
Glutathione and Fuel Oxidation in Aging
Glutathione is an important antioxidant protein which protects cells from harmful oxidative stress. Elderly humans are known to have elevated oxidative stress and deficiency of glutathione, but it is not known whether there is deficient synthesis of glutathione in muscle tissue of elderly humans.
Mitochondria are engines of cells where food consumed is burned to make energy. Under normal conditions the fuel of choice in the fasted state is fat, but fasted elderly humans are not able to oxidize fat as well as healthy young humans. Elderly humans also have the highest incidence and prevalence of being overweight and obese, and have increased storage of fat in liver and muscle.
This study will help determine whether
- elderly humans have diminished synthesis of glutathione in the skeletal muscle, and whether this can be improved by supplementing cysteine and glycine (and not an isonitrogenous placebo) in the diet;
- improving muscle glutathione concentrations can also improve fuel oxidation in aging;
- improvement of intracellular glutathione concentrations will be associated with a change in total body fat content
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Subjects will be recruited by written informed consent on forms approved by the Institutional Review Board of Baylor College of Medicine at the time of approval of the full protocol. Subjects taking an nonvitamin supplements or lipid lowering medications will stop this 4 weeks before the screening labs and for the entire duration of the study. Fasted subjects will have screening labs (blood count, HbA1c, lipid profile, liver profile, blood urea nitrogen, Creatinine, thyroid stimulating hormone, free t4, cortisol) followed by an oral glucose tolerance test, measures of muscle strength by dynamometry, tests of function (including a 6-min walk test) and body composition scans to measure total body fat. On another occasion, fasted subjects will be undergo stable isotope infusions and other studies in the metabolic research unit to measure concentrations of amino-acids and glutathione in red blood cells and muscle tissue, glutathione synthesis rates in muscle and red cells, plasma and whole-body mitochondrial fatty-acid oxidation, Kreb's cycle function, urine urea nitrogen, plasma reactive oxygen species and F2-isoprostanes, genes of glutathione synthesis and fuel oxidation. Elderly subjects will also have magnetic resonance spectroscopy scan for liver and muscle fat content.
Young subjects will be given dietary cysteine and glycine for 2-weeks and be restudied 2-weeks later. They are then released from the study.
Elderly subjects will be studied for 16 weeks. They will be assigned to receive either cysteine plus glycine, or alanine in a randomized, double-blinded study design. The studies described above will be repeated after 2 weeks and 16 weeks. Subjects will have monthly measures of liver profile, lipid profiles, BUN and creatinine and glutathione.
Study Type
Enrollment (Anticipated)
Phase
- Early Phase 1
Contacts and Locations
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030
- Baylor College of Medicine
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Elderly subjects: age range 61-80y.
- Young healthy subjects: age range 21-40y
Exclusion Criteria:
- Renal impairment (serum creatinine >1.5 mg/dL)
- Liver impairment (liver transaminases >2x upper limit of normal)
- Untreated/uncontrolled hyperthyroidism or hypothyroidism
- Known hypercortisolemia
- Known diabetes mellitus
- Hospitalization in the past 3 months
- BMI <27 (elderly group)
- Elderly women on estrogen replacement
- Known pre-existing coronary artery disease
- Fasted plasma triglyceride >300 mg/dl (on lipid lowering medications)
- Fasted plasma triglyceride >500 mg/dl (off lipid lowering medications)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Young controls
Young controls will be studied before and after receiving cysteine and glycine for 2 weeks
|
Young controls will receive cysteine plus glycine for 2 weeks The elderly subjects will be randomized in a double-blinded design to receive either cysteine plus glycine OR alanine for a period of 4 months |
Active Comparator: Elderly active
Elderly subjects in the active group will receive glycine plus cysteine (as n-acetylcysteine) for 4 months, and be studied at baseline, 2 weeks and 4 months
|
Young controls will receive cysteine plus glycine for 2 weeks The elderly subjects will be randomized in a double-blinded design to receive either cysteine plus glycine OR alanine for a period of 4 months |
Placebo Comparator: Elderly placebo
Elderly subjects in the placebo group will receive alanine for 4 months, and be studied at baseline, 2 weeks and 4 months
|
Young controls will receive cysteine plus glycine for 2 weeks The elderly subjects will be randomized in a double-blinded design to receive either cysteine plus glycine OR alanine for a period of 4 months |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Muscle glutathione concentration
Time Frame: Each subject will be studied over 4 months
|
Each subject will be studied over 4 months
|
Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Protective Agents
- Respiratory System Agents
- Antioxidants
- Antidotes
- Free Radical Scavengers
- Expectorants
- Glycine Agents
- Acetylcysteine
- N-monoacetylcystine
- Glycine
Other Study ID Numbers
- H-30681 GSH-Aging
- R01AG041782 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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