AgingEarly Phase 1NCT01870193
Glutathione and Fuel Oxidation in Aging
A Early Phase 1 study testing Glycine, cysteine (as n-acetylcysteine), alanine in people with Aging, run by Rajagopal V Sekhar at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 21 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Aging
- What is being tested?
- Glycine, cysteine (as n-acetylcysteine), alanine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Apr 2013to 22 Aug 2022
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Elderly subjects: age range 61-80y.
- Young healthy subjects: age range 21-40y
Who cannot join
- 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
Show all 11Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read more
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
Read the 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.
- Conditions
- Aging
- Being tested
- Glycine, cysteine (as n-acetylcysteine), alanine
- Keywords
- Glutathione deficiency in aging, Impaired mitochondrial fatty-acid oxidation in aging
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Glycine, cysteine (as n-acetylcysteine), alanineDietary supplement
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
| Study group | Role | What they receive |
|---|---|---|
| Young controls | Active comparator | Young controls will be studied before and after receiving cysteine and glycine for 2 weeks Receives: Dietary Supplement: Glycine, cysteine (as n-acetylcysteine), alanine |
| Elderly active | Active comparator | 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 Receives: Dietary Supplement: Glycine, cysteine (as n-acetylcysteine), alanine |
| Elderly placebo | Placebo comparator | Elderly subjects in the placebo group will receive alanine for 4 months, and be studied at baseline, 2 weeks and 4 months Receives: Dietary Supplement: Glycine, cysteine (as n-acetylcysteine), alanine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Muscle glutathione concentration
Measured: Each subject will be studied over 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2013 (estimated)
- Study start23 Apr 2013
- Primary completionMar 2019
- Study completion22 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AgingStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Rajagopal V Sekhar
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor-investigator, Rajagopal V Sekhar, Baylor College of Medicine
- Investigators
- R V Sekhar, MD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01870193
- Sponsor's protocol ID
- H-30681 GSH-Aging
- Other IDs
- R01AG041782
- Status last verified
- Feb 2023
- First submitted
- 30 May 2013
- Last updated
- 15 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Kumar P, Liu C, Suliburk J, Hsu JW, Muthupillai R, Jahoor F, Minard CG, Taffet GE, Sekhar RV. Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial. J Gerontol A Biol Sci Med Sci. 2023 Jan 26;78(1):75-89. doi: 10.1093/gerona/glac135.
PubMed 35975308
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Glutathione and Fuel Oxidation in Aging
- ClinicalTrials.gov ID
- NCT01870193
- Acronym / sponsor ID
- H-30681 GSH-Aging
- Conditions
- Aging
- Keywords
- Glutathione deficiency in aging, Impaired mitochondrial fatty-acid oxidation in aging
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Rajagopal V SekharUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 23 Apr 2013 (actual)
- Primary completion
- Mar 2019 (actual)
- Study completion
- 22 Aug 2022 (actual)
- First posted
- 5 Jun 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Young controls | Active comparator | Dietary Supplement: Glycine, cysteine (as n-acetylcysteine), alanineYoung controls will be studied before and after receiving cysteine and glycine for 2 weeks |
| Elderly active | Active comparator | Dietary Supplement: Glycine, cysteine (as n-acetylcysteine), alanineElderly 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 |
| Elderly placebo | Placebo comparator | Dietary Supplement: Glycine, cysteine (as n-acetylcysteine), alanineElderly subjects in the placebo group will receive alanine for 4 months, and be studied at baseline, 2 weeks and 4 months |
Who may qualify
- Ages
- 21 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Elderly subjects: age range 61-80y.
- Young healthy subjects: age range 21-40y
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Glycine, cysteine (as n-acetylcysteine), alanineYoung 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 | Dietary supplement | Elderly active, Elderly placebo, Young controls |
Primary outcome
Muscle glutathione concentration
Time frame: Each subject will be studied over 4 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2023.
- Derived from this study: PubMed 35975308Kumar P, Liu C, Suliburk J, Hsu JW, Muthupillai R, Jahoor F, Minard CG, Taffet GE, Sekhar RV. Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial. J Gerontol A Biol Sci Med Sci. 2023 Jan 26;78(1):75-89. doi: 10.1093/gerona/glac135.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
R V Sekhar, MD principal investigator
Baylor College of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Glycine, cysteine (as n-acetylcysteine), alanine in people with Aging, run by Rajagopal V Sekhar at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Muscle glutathione concentration (time frame: Each subject will be studied over 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01870193, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2023.