Role of HIV on Glutathione Synthesis and Oxidative Stress

Phase 1

Completed

• Conditions: HIV Infection; Erythrocyte Glutathione Deficiency
• Interventions: Dietary Supplement: Cysteine (as n-acetylcysteine) and glycine; Dietary Supplement: Cysteine/glycine

• Registration Number: NCT01355198
• Lead Sponsor: Baylor College of Medicine

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-08
• Study First Submitted: 2011-03-30
• Study First Submitted QC: 2011-05-17
• Study First Posted: 2011-05-18
• Primary Completion: 2011-09
• Study Completion: 2011-09
• Status Verified: 2013-02
• Last Update Submitted: 2013-02-05
• Last Update Posted: 2013-02-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 10

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

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Glutathione synthesis rates and concentrations	9 hours	Fractional and absolute synthesis rates of glutathione and its concentrations

Secondary Outcome Measures

Name	Time	Method
Muscle strength	Done once in each 9-hour study
Quality of life by SF36 questionnaire	Before and after
Mitochondrial fuel oxidation	Twice over 9 hours of the study on 2 occassions	Lipolysis, fuel oxidation, and a hyperinsulinemic euglycemic clamp.
Rates of fuel kinetics	3 hours	Measure rate of lipolysis (from infused 13C-palmitate) and recovery of 13CO2 (from infused acetate tracer)
Insulin sensitivity	3 hours	Measure insulin sensitivity using a hyperglycemic euglycemic clamp

Trial Locations

Locations (1)

Baylor GCRC; 🇺🇸 Houston, Texas, United States