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

HIV Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01962961
• Other study ID #: IU SRI 1306011647
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: October 11, 2013
• Last updated: January 11, 2016
• Start date: October 2013
• Est. completion date: October 2015

Study information

• Verified date: December 2015
• Source: Indiana University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: October 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Endothelial Dysfunction
• HIV
• Oxidative Stress

Intervention

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).
• Matching placebo
Inactive pill that matches PharmaNAC on taste, color, and appearance.

Locations

Country	Name	City	State
United States	Indiana University Health University Hospital, Indiana Clinical Research Center	Indianapolis	Indiana

Sponsors (2)

Lead Sponsor	Collaborator
Indiana University	BioAdvantex Pharma

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Circulating Malondialdehyde Levels	Measure of oxidative stress	Baseline and 8 weeks	No
Primary	Change in Circulating F2-isoprostane Levels	Oxidative stress measure	Baseline and 8 weeks	No
Primary	Change in Flow-mediated Dilation (FMD) of the Brachial Artery	Measure of endothelial function	Baseline and 8 weeks	No