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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Indiana University
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Change in Circulating F2-isoprostane Levels
Study Overview
Brief Summary
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.
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 50 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
PharmaNAC 1800 mg
PharmaNAC 900 mg orally twice daily for 8 weeks
Intervention: PharmaNAC (N-acetylcysteine) (Dietary Supplement)
PharmaNAC 1800 mg
PharmaNAC 900 mg orally twice daily for 8 weeks
Intervention: Matching placebo (Dietary Supplement)
PharmaNAC 3600 mg
PharmaNAC 1800 mg orally twice daily for 8 weeks
Intervention: PharmaNAC (N-acetylcysteine) (Dietary Supplement)
Placebo
Matching placebo pills given twice daily for 8 weeks
Intervention: Matching placebo (Dietary Supplement)
Outcomes
Primary Outcomes
Change in Circulating F2-isoprostane Levels
Time Frame: Baseline and 8 weeks
Oxidative stress measure
Change in Flow-mediated Dilation (FMD) of the Brachial Artery
Time Frame: Baseline and 8 weeks
Measure of endothelial function
Change in Circulating Malondialdehyde Levels
Time Frame: Baseline and 8 weeks
Measure of oxidative stress
Secondary Outcomes
No secondary outcomes reported
Investigators
Samir K Gupta, MD, MS
Associate Professor of Medicine
Indiana University