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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
  Purpose

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.


Condition Intervention Phase
HIV Infection
Erythrocyte Glutathione Deficiency
Dietary Supplement: Cysteine (as n-acetylcysteine) and glycine
Dietary Supplement: Cysteine/glycine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Role of HIV on Glutathione Synthesis and Oxidative Stress

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • Glutathione synthesis rates and concentrations [ Time Frame: 9 hours ] [ Designated as safety issue: No ]
    Fractional and absolute synthesis rates of glutathione and its concentrations


Secondary Outcome Measures:
  • 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 ]

Enrollment: 10
Study Start Date: August 2010
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cysteine/glycine
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
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)

  Eligibility

Ages Eligible for Study:   21 Years to 70 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01355198

Locations
United States, Texas
Baylor GCRC
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor College of Medicine
Investigators
Principal Investigator: R V Sekhar, MD Baylor College of Medicine
  More Information

No publications provided

Responsible Party: Rajagopal Sekhar, Associate Professor, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT01355198     History of Changes
Other Study ID Numbers: HIV and glutathione
Study First Received: March 30, 2011
Last Updated: February 5, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Acetylcysteine
Glycine
N-monoacetylcystine
Anti-Infective Agents
Antidotes
Antioxidants
Antiviral Agents
Expectorants
Free Radical Scavengers
Glycine Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 19, 2014