Clinical trial NCT01355198: Role of HIV on Glutathione Synthesis and Oxidative Stress
Official title: Role of HIV on Glutathione Synthesis and Oxidative Stress
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infection
Erythrocyte Glutathione Deficiency
Lead sponsor: Baylor College of Medicine
Sponsor class: OTHER
First posted: 2011-05-18
Enrollment: 10
Sex: MALE
Minimum age (years): 21
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Glutathione synthesis rates and concentrations
timeFrame: 9 hours
Secondary outcomes:
measure: Mitochondrial fuel oxidation
timeFrame: Twice over 9 hours of the study on 2 occassions
measure: Rates of fuel kinetics
timeFrame: 3 hours
measure: Insulin sensitivity
timeFrame: 3 hours
measure: Muscle strength
timeFrame: Done once in each 9-hour study
measure: Quality of life by SF36 questionnaire
timeFrame: Before and after
Other outcomes:
Locations:
city: Houston
country: United States
facility: Baylor GCRC
state: Texas
Study officials:
affiliation: Baylor College of Medicine
name: R V Sekhar, MD
role: PRINCIPAL_INVESTIGATOR
References: