Role of HIV on Glutathione Synthesis and Oxidative Stress

NCT ID: NCT01355198

Last Updated: 2013-02-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-08-31
• Study Completion Date: 2011-09-30

Brief 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. 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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cysteine/glycine

Subjects will be studied before and after receiving oral cysteine (as n-acetylcysteine) and glycine for 2 weeks

Group Type: EXPERIMENTAL

Cysteine (as n-acetylcysteine) and glycine

Intervention Type: DIETARY_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/glycine

Intervention Type: DIETARY_SUPPLEMENT

Subjects will receive oral dietary amino-acids (cystiene as n-acetylcysteine, and glycine)

Interventions

Cysteine (as n-acetylcysteine) and glycine

Cysteine and glycine will be supplemented at doses of 0.81 mmol/kg/d and 1.31 mmol/kg/d for 2 weeks each

Intervention Type: DIETARY_SUPPLEMENT

Cysteine/glycine

Subjects will receive oral dietary amino-acids (cystiene as n-acetylcysteine, and glycine)

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

(1) HIV infected patients with GSH deficiency

Exclusion Criteria

1. renal impairment (serum Creatinine above 1.5mg/dL), liver impairment (ALT and AST > 2x upper limit of normal)

2. any hormonal disorders such as hypothyroidism, hypercortisolemia, hypogonadism, or diabetes mellitus on pharmacotherapy

3. evidence of infections other than HIV in the preceding 3 months

4. subjects with plasma triglyceride concentrations of ≥ 500mg/dL on triglyceride lowering therapy

5. BMI < 20

6. established heart disease

7. Co-existing viral hepatitis B and C

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Baylor College of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Rajagopal Sekhar

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

R V Sekhar, MD

Role: PRINCIPAL_INVESTIGATOR

Baylor College of Medicine

Locations

Baylor GCRC

Houston, Texas, United States

Countries

United States

Other Identifiers

HIV and glutathione

Identifier Type: -

Identifier Source: org_study_id