Role of HIV on Glutathione Synthesis and Oxidative Stress

HIV Infection Clinical Trial

Official title:

Role of HIV on Glutathione Synthesis and Oxidative Stress

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01355198
• Other study ID #: HIV and glutathione
• Status: Completed
• Phase: Phase 1
• First received: March 30, 2011
• Last updated: February 5, 2013
• Start date: August 2010
• Est. completion date: September 2011

Study information

• Verified date: February 2013
• Source: Baylor College of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: September 2011
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 21 Years to 70 Years

Eligibility

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

Study Design

Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Erythrocyte Glutathione Deficiency
• HIV Infection

Intervention

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

Locations

Country	Name	City	State
United States	Baylor GCRC	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Baylor College of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glutathione synthesis rates and concentrations	Fractional and absolute synthesis rates of glutathione and its concentrations	9 hours	No
Secondary	Mitochondrial fuel oxidation	Lipolysis, fuel oxidation, and a hyperinsulinemic euglycemic clamp.	Twice over 9 hours of the study on 2 occassions	No
Secondary	Rates of fuel kinetics	Measure rate of lipolysis (from infused 13C-palmitate) and recovery of 13CO2 (from infused acetate tracer)	3 hours	No
Secondary	Insulin sensitivity	Measure insulin sensitivity using a hyperglycemic euglycemic clamp	3 hours	No
Secondary	Muscle strength		Done once in each 9-hour study	No
Secondary	Quality of life by SF36 questionnaire		Before and after	No