Glutathione and Fuel Oxidation in Aging

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Baylor College of Medicine
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Rajagopal V Sekhar, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT01870193
First received: May 30, 2013
Last updated: April 4, 2014
Last verified: April 2014
  Purpose

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

  1. 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;
  2. improving muscle glutathione concentrations can also improve fuel oxidation in aging;
  3. improvement of intracellular glutathione concentrations will be associated with a change in total body fat content

Condition Intervention
Aging
Dietary Supplement: Glycine, cysteine (as n-acetylcysteine), alanine

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Glutathione and Fuel Oxidation in Aging

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • Muscle glutathione concentration [ Time Frame: Each subject will be studied over 4 months ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Breath, blood and muscle tissue


Estimated Enrollment: 36
Study Start Date: October 2012
Estimated Study Completion Date: August 2017
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Young controls
Young controls will be studied before and after receiving cysteine and glycine for 2 weeks
Dietary Supplement: Glycine, cysteine (as n-acetylcysteine), alanine

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

Elderly group
Elderly subjects will be randomized in a double-blinded design to receive either cysteine plus glycine or alanine for 4 months, and be studied at baseline, 2 weeks and 4 months
Dietary Supplement: Glycine, cysteine (as n-acetylcysteine), alanine

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


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.

  Eligibility

Ages Eligible for Study:   21 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Community sample

Criteria

Inclusion Criteria:

  1. Elderly subjects: age range 61-80y.
  2. Young healthy subjects: age range 21-40y

Exclusion Criteria:

  1. Renal impairment (serum creatinine >1.5 mg/dL)
  2. Liver impairment (liver transaminases >2x upper limit of normal)
  3. Untreated/uncontrolled hyperthyroidism or hypothyroidism
  4. Known hypercortisolemia
  5. Known diabetes mellitus
  6. Hospitalization in the past 3 months
  7. BMI <27 (elderly group)
  8. Elderly women on estrogen replacement
  9. Known pre-existing coronary artery disease
  10. Fasted plasma triglyceride >300 mg/dl (on lipid lowering medications)
  11. Fasted plasma triglyceride >500 mg/dl (off lipid lowering medications)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01870193

Locations
United States, Texas
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: R V Sekhar, MD    713-798-4951      
Principal Investigator: R V Sekhar, MD         
Sponsors and Collaborators
Rajagopal V Sekhar
Investigators
Principal Investigator: R V Sekhar, MD Baylor College of Medicine
  More Information

No publications provided

Responsible Party: Rajagopal V Sekhar, Associate Professor, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT01870193     History of Changes
Other Study ID Numbers: GSH-Aging, R01AG041782
Study First Received: May 30, 2013
Last Updated: April 4, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Baylor College of Medicine:
Glutathione deficiency in aging
Impaired mitochondrial fatty-acid oxidation in aging

Additional relevant MeSH terms:
Acetylcysteine
Glycine
N-monoacetylcystine
Anti-Infective Agents
Antidotes
Antioxidants
Antiviral Agents
Expectorants
Free Radical Scavengers
Glycine Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014