Clinical trial NCT01962961: N-acetylcysteine to Reduce Oxidative Stress and Improve Endothelial Function in HIV-infected Older Adults
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: HIV
Endothelial Dysfunction
Oxidative Stress
Keywords: HIV
Endothelial function
Oxidative stress
Cardiovascular disease
N-acetylcysteine
Lead sponsor: Indiana University
Sponsor class: OTHER
Collaborators: name: BioAdvantex Pharma
First posted: 2013-10-16
Enrollment: 24
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Change in Circulating Malondialdehyde Levels
timeFrame: Baseline and 8 weeks
measure: Change in Circulating F2-isoprostane Levels
timeFrame: Baseline and 8 weeks
measure: Change in Flow-mediated Dilation (FMD) of the Brachial Artery
timeFrame: Baseline and 8 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University Health University Hospital, Indiana Clinical Research Center
state: Indiana
Study officials:
affiliation: Indiana University School of Medicine
name: Samir K Gupta, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: