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N-acetylcysteine to Reduce Oxidative Stress and Improve Endothelial Function in HIV-infected Older Adults

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Indiana University
Sponsor:
Collaborator:
BioAdvantex Pharma
Information provided by (Responsible Party):
Samir K Gupta, MD, MS, Indiana University
ClinicalTrials.gov Identifier:
NCT01962961
First received: October 11, 2013
Last updated: April 28, 2014
Last verified: April 2014
  Purpose

The goal of this study is to determine if n-acetylcysteine, given as PharmaNAC, reduces oxidative stress and improves vascular function in HIV-infected older adults already on HIV treatment.


Condition Intervention Phase
HIV
Endothelial Dysfunction
Oxidative Stress
Dietary Supplement: PharmaNAC (N-acetylcysteine)
Dietary Supplement: Matching placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Placebo-Controlled Pilot Trial Assessing Two Doses of N-Acetylcysteine on Changes in Oxidative Stress and Endothelial Function in HIV-infected Older Adults Receiving Stable Antiretroviral Therapy

Resource links provided by NLM:


Further study details as provided by Indiana University:

Primary Outcome Measures:
  • Circulating malondialdehyde levels [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Measure of oxidative stress

  • Circulating F2-isoprostane levels [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Oxidative stress measure

  • Flow-mediated dilation (FMD) of the brachial artery [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Measure of endothelial function


Secondary Outcome Measures:
  • Adverse events [ Time Frame: 4 week and 8 weeks ] [ Designated as safety issue: Yes ]
    Safety measures of PharmaNAC given at two different doses


Estimated Enrollment: 30
Study Start Date: October 2013
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PharmaNAC 1800 mg
PharmaNAC 900 mg orally twice daily for 8 weeks
Dietary Supplement: PharmaNAC (N-acetylcysteine)

PharmaNAC is considered a nutritional supplement and can be obtained without a prescription. All participants will be asked to ingest two tablets twice per day during this trial. For those randomized to PharmaNAC 1800 mg twice daily, this will be two active tablets twice per day. For those randomized to PharmaNAC 900 mg twice daily, this will be one active tablet twice per day and one matching placebo tablet twice per day. For those randomized to placebo, this will be two matching placebo tablets twice per day.

PharmaNAC can be taken with or without food. The effervescent tablets should be dissolved in 8 oz. of water or juice prior to oral intake. Each participant will take study drug and/or matching placebo for 8 weeks (up to 60 days).

Other Names:
  • N-acetylcysteine
  • NAC
Dietary Supplement: Matching placebo
Experimental: PharmaNAC 3600 mg
PharmaNAC 1800 mg orally twice daily for 8 weeks
Dietary Supplement: PharmaNAC (N-acetylcysteine)

PharmaNAC is considered a nutritional supplement and can be obtained without a prescription. All participants will be asked to ingest two tablets twice per day during this trial. For those randomized to PharmaNAC 1800 mg twice daily, this will be two active tablets twice per day. For those randomized to PharmaNAC 900 mg twice daily, this will be one active tablet twice per day and one matching placebo tablet twice per day. For those randomized to placebo, this will be two matching placebo tablets twice per day.

PharmaNAC can be taken with or without food. The effervescent tablets should be dissolved in 8 oz. of water or juice prior to oral intake. Each participant will take study drug and/or matching placebo for 8 weeks (up to 60 days).

Other Names:
  • N-acetylcysteine
  • NAC
Placebo Comparator: Placebo
Matching placebo pills given twice daily for 8 weeks
Dietary Supplement: Matching placebo

Detailed Description:

The primary objective of this study is to compare 8-week changes in circulating levels of malondialdehyde (MDA), circulating levels of F2-isoprostanes, and flow-mediated dilation (FMD) of the brachial artery in older HIV-infected adults already receiving virologically suppressive antiretroviral therapy (ART) who are then randomized to either NAC 900 mg twice daily, NAC 1800 mg twice daily, or placebo. The relative efficacy and safety of these two doses of NAC will be assessed.

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV-1 infection, documented by (1) any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or (2) by two detectable HIV-1 antigens, or (3) two detectable plasma HIV-1 RNA viral loads.
  • Age equal to or greater than 50 years.
  • Receipt of antiretroviral therapy of any kind for at least 6 months prior to screening.
  • HIV-1 RNA level < 75 copies/mL at screening.
  • For women who are still of reproductive potential, a negative urine pregnancy test at screening and willingness to use two forms of birth control during the course of the study. Acceptable forms of birth control include condoms (with or without a gel that can kill sperm), a diaphragm or cervical cap (with or without a gel that can kill sperm), an intrauterine device (IUD), or hormonal-based birth control ("the pill").

Exclusion Criteria:

  • Inability to complete written, informed consent.
  • Incarceration at the time of any study visit.
  • Known allergy or intolerance to n-acetylcysteine.
  • Use of n-acetylcysteine within 180 days of screening.
  • Diagnosed vascular disease (history of angina pectoris, coronary disease, peripheral vascular disease, cerebrovascular disease, aortic aneurysm, or otherwise known atherosclerotic disease).
  • History of congestive heart failure even if currently compensated.
  • History of portal hypertension or hepatic cirrhosis (either clinically diagnosed or histologically diagnosed).
  • Diagnosed disease or process, besides HIV infection, associated with increased systemic inflammation (including, but not limited to, systemic lupus erythematosis, inflammatory bowel diseases, other collagen vascular diseases).
  • Known or suspected malignancy requiring systemic treatment within six months of screening.
  • History of ADA-defined diabetes mellitus (115)
  • History of migraine headaches.
  • History of Raynaud's phenomenon.
  • History of cardiac arrhythmias or cardiomyopathy.
  • Uncontrolled hyperthyroidism or hypothyroidism, defined as TSH values outside of the local reference range on most recent clinical assessment.
  • Asthma or COPD requiring daily use of beta-2-agonist therapy (e.g. albuterol)
  • History of carotid bruits.
  • Creatinine clearance < 50 mL/min (using the Cockcroft-Gault equation) using a serum creatinine level measured at screening.
  • Hemoglobin < 9.0 g/dL at screening.
  • Alanine aminotransferase (ALT) level or aspartate aminotransferase (AST) > 3 times ULN at screening.
  • Total bilirubin > 2.5 times ULN at screening; if the participant is receiving atazanavir, then s/he would be excluded if total bilirubin is > 3.5 times ULN at screening.
  • Therapy for serious medical illnesses within 14 days prior to screening.
  • Pregnancy or breastfeeding during the course of the study.
  • Uncontrolled hypertension, defined as systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg at screening.
  • Receipt of investigational agents, cytotoxic chemotherapy, systemic glucocorticoids (of any dose), or anabolic steroids at screening.
  • Previous receipt of stavudine or didanosine for more than 7 cumulative days.
  • Receipt of daily Vitamin C or Vitamin E supplements at screening.
  • Alcohol intake more than the equivalent of one 8 oz. of wine daily for the 7 days prior to screening.
  • Active drug use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
  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: NCT01962961

Contacts
Contact: Paula Johnson, NP 317-278-2945 johnpaul@iu.edu

Locations
United States, Indiana
Indiana University Health University Hospital, Indiana Clinical Research Center Recruiting
Indianapolis, Indiana, United States, 46202
Sponsors and Collaborators
Indiana University
BioAdvantex Pharma
Investigators
Principal Investigator: Samir K Gupta, MD, MS Indiana University School of Medicine
  More Information

No publications provided

Responsible Party: Samir K Gupta, MD, MS, Associate Professor of Medicine, Indiana University
ClinicalTrials.gov Identifier: NCT01962961     History of Changes
Other Study ID Numbers: IU SRI 1306011647
Study First Received: October 11, 2013
Last Updated: April 28, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Indiana University:
HIV
Endothelial function
Oxidative stress
Cardiovascular disease
N-acetylcysteine

Additional relevant MeSH terms:
Acetylcysteine
N-monoacetylcystine
Anti-Infective Agents
Antidotes
Antioxidants
Antiviral Agents
Expectorants
Free Radical Scavengers
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014