Role of HIV on Glutathione Synthesis and Oxidative Stress

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Rajagopal Sekhar, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT01355198
First received: March 30, 2011
Last updated: February 5, 2013
Last verified: February 2013

March 30, 2011
February 5, 2013
August 2010
September 2011   (final data collection date for primary outcome measure)
Glutathione synthesis rates and concentrations [ Time Frame: 9 hours ] [ Designated as safety issue: No ]
Fractional and absolute synthesis rates of glutathione and its concentrations
Glutathione synthesis rates [ Time Frame: Over 8 hours ] [ Designated as safety issue: No ]
Fractional and absolute synthesis rates of glutathione
Complete list of historical versions of study NCT01355198 on ClinicalTrials.gov Archive Site
  • Mitochondrial fuel oxidation [ Time Frame: Twice over 9 hours of the study on 2 occassions ] [ Designated as safety issue: No ]
    Lipolysis, fuel oxidation, and a hyperinsulinemic euglycemic clamp.
  • Rates of fuel kinetics [ Time Frame: 3 hours ] [ Designated as safety issue: No ]
    Measure rate of lipolysis (from infused 13C-palmitate) and recovery of 13CO2 (from infused acetate tracer)
  • Insulin sensitivity [ Time Frame: 3 hours ] [ Designated as safety issue: No ]
    Measure insulin sensitivity using a hyperglycemic euglycemic clamp
  • Muscle strength [ Time Frame: Done once in each 9-hour study ] [ Designated as safety issue: No ]
  • Quality of life by SF36 questionnaire [ Time Frame: Before and after ] [ Designated as safety issue: No ]
Lipid kinetics and insulin sensitivity [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
Lipolysis, fat oxidation and adipocyte and hepatic re-estrification rates, and a hyperinsulinemic euglycemic clamp.
Not Provided
Not Provided
 
Role of HIV on Glutathione Synthesis and Oxidative Stress
Role of HIV on Glutathione Synthesis and Oxidative Stress

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.

Not Provided
Interventional
Phase 1
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • HIV Infection
  • Erythrocyte Glutathione Deficiency
  • Dietary Supplement: 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
  • Dietary Supplement: Cysteine/glycine
    Subjects will receive oral dietary amino-acids (cystiene as n-acetylcysteine, and glycine)
Experimental: Cysteine/glycine
Subjects will be studied before and after receiving oral cysteine (as n-acetylcysteine) and glycine for 2 weeks
Interventions:
  • Dietary Supplement: Cysteine (as n-acetylcysteine) and glycine
  • Dietary Supplement: Cysteine/glycine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
10
September 2011
September 2011   (final data collection date for primary outcome measure)

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
Male
21 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01355198
HIV and glutathione
No
Rajagopal Sekhar, Baylor College of Medicine
Baylor College of Medicine
Not Provided
Principal Investigator: R V Sekhar, MD Baylor College of Medicine
Baylor College of Medicine
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP