Role of HIV on Glutathione Synthesis and Oxidative Stress

NCT01355198 | Completed Phase 1

• 1 other identifier: HIV and glutathione
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Glutathione synthesis rates and concentrations

  Fractional and absolute synthesis rates of glutathione and its concentrations

  9 hours

Secondary Outcomes (5)

• Mitochondrial fuel oxidation

  Twice over 9 hours of the study on 2 occassions

• Rates of fuel kinetics

  3 hours

• Insulin sensitivity

  3 hours

• Muscle strength

  Done once in each 9-hour study

• Quality of life by SF36 questionnaire

  Before and after

Study Arms (1)

Cysteine/glycine

EXPERIMENTAL

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

Dietary Supplement: Cysteine (as n-acetylcysteine) and glycine; Dietary Supplement: Cysteine/glycine

Interventions

Cysteine (as n-acetylcysteine) and glycine 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

Cysteine/glycine DIETARY_SUPPLEMENT

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

Cysteine/glycine

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• (1) HIV infected patients with GSH deficiency

You may not qualify if:

• renal impairment (serum Creatinine above 1.5mg/dL), liver impairment (ALT and AST \> 2x upper limit of normal)
• any hormonal disorders such as hypothyroidism, hypercortisolemia, hypogonadism, or diabetes mellitus on pharmacotherapy
• evidence of infections other than HIV in the preceding 3 months
• subjects with plasma triglyceride concentrations of ≥ 500mg/dL on triglyceride lowering therapy
• BMI \< 20
• established heart disease
• Co-existing viral hepatitis B and C

Sponsors & Collaborators

• Baylor College of Medicine: lead

Study Sites (1)

Baylor GCRC

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

HIV Infections

Interventions

Cysteine; Glycine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Sulfhydryl Compounds; Amino Acids, Neutral; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• R V Sekhar, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: March 30, 2011
• First Posted: May 18, 2011
• Study Start: August 1, 2010
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: February 7, 2013

Record last verified: 2013-02

Locations

US (1)