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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: 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 Rajagopal Sekhar, Baylor College of Medicine:

Primary Outcome Measures:
  • Glutathione synthesis rates and concentrations [ Time Frame: 9 hours ]
    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 ]
    Lipolysis, fuel oxidation, and a hyperinsulinemic euglycemic clamp.

  • Rates of fuel kinetics [ Time Frame: 3 hours ]
    Measure rate of lipolysis (from infused 13C-palmitate) and recovery of 13CO2 (from infused acetate tracer)

  • Insulin sensitivity [ Time Frame: 3 hours ]
    Measure insulin sensitivity using a hyperglycemic euglycemic clamp

  • Muscle strength [ Time Frame: Done once in each 9-hour study ]
  • Quality of life by SF36 questionnaire [ Time Frame: Before and after ]

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   (Adult, Senior)
Sexes 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

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

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

ClinicalTrials.gov processed this record on June 23, 2017