HIV InfectionPhase 1NCT01355198
Role of HIV on Glutathione Synthesis and Oxidative Stress
A Phase 1 study testing Cysteine (as n-acetylcysteine) and glycine and Cysteine/glycine in people with HIV Infection and Erythrocyte Glutathione Deficiency, run by Baylor College of Medicine at 1 site in United States.
Trial summary
HIV infection is associated the development of increased oxidative stress and deficiency of glutathione (GSH), the dominant endogenous antioxidant protein, but the underlying mechanisms contributing to GSH deficiency are hitherto unknown. Read more about this study
- Who is it for?
- Ages 21 to 70 years, men only
- Conditions the study is for
- HIV Infection, Erythrocyte Glutathione Deficiency
- What is being tested?
- Cysteine (as n-acetylcysteine) and glycine and Cysteine/glycine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2010to Sep 2011
- Phase
- 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 70 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV infected patients with GSH deficiency
Who cannot join
- renal impairment (serum Creatinine above 1.5mg/dL), liver impairment (ALT and AST > 2x upper limit of normal)
- any hormonal disorders such as hypothyroidism, hypercortisolemia, hypogonadism, or diabetes mellitus on pharmacotherapy
- evidence of infections other than HIV in the preceding 3 months
- subjects with plasma triglyceride concentrations of ≥ 500mg/dL on triglyceride lowering therapy
- BMI < 20
- established heart disease
- Co-existing viral hepatitis B and C
Trial locations and contacts
1 site in 1 country.
About this study
HIV infection is associated the development of increased oxidative stress and deficiency of glutathione (GSH), the dominant endogenous antioxidant protein, but the underlying mechanisms contributing to GSH deficiency are hitherto unknown. Furthermore GSH metabolism has not been studied in HIV patients, in whom the burden of risk factors promoting oxidative stress is highest. Our previous studies in non-HIV human subjects with diabetes-related oxidative stress and GSH deficiency have demonstrated that the latter is due to decreased synthesis of GSH. Importantly, short-term dietary supplementation with the simple GSH precursor amino-acids cysteine and glycine, boosted GSH synthesis and cellular concentrations, corrected GSH deficiency, and reduced oxidative stress and oxidant damage. The current proposal will study whether (1) defective synthesis underlies GSH deficiency in patients with HIV, and will test a simple, inexpensive and rational therapy based on protein supplementation to improve GSH synthesis and concentrations and lower markers of oxidative stress and oxidant damage in these patients; (2) study if correction of GSH deficiency is asssociated with any changes in (a) impaired mitochondrial fuel oxidation in the fasted and insulin stimulated states; (b) insulin sensitivity; (c) body composition and anthropometry; (d) forearm muscle strength; (e) plasma biochemistry, and (f) quality of life indices in these subjects.
- Conditions
- HIV Infection, Erythrocyte Glutathione Deficiency
- Being tested
- Cysteine (as n-acetylcysteine) and glycine, Cysteine/glycine
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cysteine (as n-acetylcysteine) and glycineDietary supplement
Cysteine and glycine will be supplemented at doses of 0.81 mmol/kg/d and 1.31 mmol/kg/d for 2 weeks each
Cysteine/glycineDietary supplement
Subjects will receive oral dietary amino-acids (cystiene as n-acetylcysteine, and glycine)
| Study group | Role | What they receive |
|---|---|---|
| Cysteine/glycine | Experimental | Subjects will be studied before and after receiving oral cysteine (as n-acetylcysteine) and glycine for 2 weeks Receives: Dietary Supplement: Cysteine (as n-acetylcysteine) and glycine; Dietary Supplement: Cysteine/glycine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glutathione synthesis rates and concentrations
Fractional and absolute synthesis rates of glutathione and its concentrations
Measured: 9 hours
Secondary outcomes (5)
Mitochondrial fuel oxidation
Lipolysis, fuel oxidation, and a hyperinsulinemic euglycemic clamp.
Measured: Twice over 9 hours of the study on 2 occassions
Rates of fuel kinetics
Measure rate of lipolysis (from infused 13C-palmitate) and recovery of 13CO2 (from infused acetate tracer)
Measured: 3 hours
Insulin sensitivity
Measure insulin sensitivity using a hyperglycemic euglycemic clamp
Measured: 3 hours
Muscle strength
Measured: Done once in each 9-hour study
Quality of life by SF36 questionnaire
Measured: Before and after
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2011 (estimated)
- Study startAug 2010
- Primary completionSep 2011
- Study completionSep 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe sponsor's other registered studies.
- 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
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rajagopal Sekhar, Baylor College of Medicine
- Investigators
- R V Sekhar, MD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01355198
- Sponsor's protocol ID
- HIV and glutathione
- Status last verified
- Feb 2013
- First submitted
- 30 Mar 2011
- Last updated
- 7 Feb 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of HIV on Glutathione Synthesis and Oxidative Stress
- ClinicalTrials.gov ID
- NCT01355198
- Acronym / sponsor ID
- HIV and glutathione
- Conditions
- HIV Infection, Erythrocyte Glutathione Deficiency
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Study start
- Aug 2010
- Primary completion
- Sep 2011 (actual)
- Study completion
- Sep 2011 (actual)
- First posted
- 18 May 2011 (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.
HIV infection is associated the development of increased oxidative stress and deficiency of glutathione (GSH), the dominant endogenous antioxidant protein, but the underlying mechanisms contributing to GSH deficiency are hitherto unknown. Furthermore GSH metabolism has not been studied in HIV patients, in whom the burden of risk factors promoting oxidative stress is highest. Our previous studies in non-HIV human subjects with diabetes-related oxidative stress and GSH deficiency have demonstrated that the latter is due to decreased synthesis of GSH. Importantly, short-term dietary supplementation with the simple GSH precursor amino-acids cysteine and glycine, boosted GSH synthesis and cellular concentrations, corrected GSH deficiency, and reduced oxidative stress and oxidant damage. The current proposal will study whether (1) defective synthesis underlies GSH deficiency in patients with HIV, and will test a simple, inexpensive and rational therapy based on protein supplementation to improve GSH synthesis and concentrations and lower markers of oxidative stress and oxidant damage in these patients; (2) study if correction of GSH deficiency is asssociated with any changes in (a) impaired mitochondrial fuel oxidation in the fasted and insulin stimulated states; (b) insulin sensitivity; (c) body composition and anthropometry; (d) forearm muscle strength; (e) plasma biochemistry, and (f) quality of life indices in these subjects.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cysteine/glycine | Experimental | Dietary Supplement: Cysteine (as n-acetylcysteine) and glycine, Dietary Supplement: Cysteine/glycineSubjects will be studied before and after receiving oral cysteine (as n-acetylcysteine) and glycine for 2 weeks |
Who may qualify
- Ages
- 21 to 70 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- HIV infected patients with GSH deficiency
Key exclusion criteria (7 listed)
- renal impairment (serum Creatinine above 1.5mg/dL), liver impairment (ALT and AST > 2x upper limit of normal)
- any hormonal disorders such as hypothyroidism, hypercortisolemia, hypogonadism, or diabetes mellitus on pharmacotherapy
- evidence of infections other than HIV in the preceding 3 months
- subjects with plasma triglyceride concentrations of ≥ 500mg/dL on triglyceride lowering therapy
- BMI < 20
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 |
|---|---|---|
| Cysteine (as n-acetylcysteine) and glycineCysteine and glycine will be supplemented at doses of 0.81 mmol/kg/d and 1.31 mmol/kg/d for 2 weeks each | Dietary supplement | Cysteine/glycine |
| Cysteine/glycineSubjects will receive oral dietary amino-acids (cystiene as n-acetylcysteine, and glycine) | Dietary supplement | Cysteine/glycine |
Primary outcome
Glutathione synthesis rates and concentrations
Time frame: 9 hours
Fractional and absolute synthesis rates of glutathione and its concentrations
5 secondary outcomes
Mitochondrial fuel oxidation
Time frame: Twice over 9 hours of the study on 2 occassions
Rates of fuel kinetics
Time frame: 3 hours
Insulin sensitivity
Time frame: 3 hours
Muscle strength
Time frame: Done once in each 9-hour study
Quality of life by SF36 questionnaire
Time frame: Before and after
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 7 Feb 2013.
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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 Phase 1 study testing Cysteine (as n-acetylcysteine) and glycine and Cysteine/glycine in people with HIV Infection and Erythrocyte Glutathione Deficiency, run by Baylor College of Medicine 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 1 inclusion and 7 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 7 Feb 2013. 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. 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?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Glutathione synthesis rates and concentrations (time frame: 9 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Feb 2013.