N-acetylcysteine to Reduce Oxidative Stress and Improve E... | NCT01962961

NCT01962961

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Name	Class
BioAdvantex Pharma	UNKNOWN

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
PharmaNAC 1800 mg	Experimental	PharmaNAC 900 mg orally twice daily for 8 weeks	Dietary Supplement: PharmaNAC (N-acetylcysteine) Dietary Supplement: Matching placebo
PharmaNAC 3600 mg	Experimental	PharmaNAC 1800 mg orally twice daily for 8 weeks	Dietary Supplement: PharmaNAC (N-acetylcysteine)
Placebo	Placebo Comparator	Matching placebo pills given twice daily for 8 weeks	Dietary Supplement: Matching placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
PharmaNAC (N-acetylcysteine)	Dietary Supplement	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).

Measure	Description	Time Frame
Change in Circulating Malondialdehyde Levels	Measure of oxidative stress	Baseline and 8 weeks
Change in Circulating F2-isoprostane Levels	Oxidative stress measure	Baseline and 8 weeks
Change in Flow-mediated Dilation (FMD) of the Brachial Artery	Measure of endothelial function	Baseline and 8 weeks

Eligibility Module

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.

Name	Affiliation	Role
Samir K Gupta, MD, MS	Indiana University	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Indiana University Health University Hospital, Indiana Clinical Research Center		Indianapolis	Indiana	46202	United States

Arm/Group Information

ID	Title	Description
FG000	PharmaNAC 1800 mg	PharmaNAC 900 mg orally twice daily for 8 weeks 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.
FG001	PharmaNAC 3600 mg	PharmaNAC 1800 mg orally twice daily for 8 weeks 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).
FG002	Placebo	Matching placebo pills given twice daily for 8 weeks Matching placebo: Inactive pill that matches PharmaNAC on taste, color, and appearance.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	PharmaNAC 1800 mg	PharmaNAC 900 mg orally twice daily for 8 weeks 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.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change in Circulating Malondialdehyde Levels

Measure of oxidative stress

Analysis population includes those who completed the 8 week trial and had both baseline and week 8 values available.

Posted

Mean

Standard Deviation

micromolar

Baseline and 8 weeks

ID	Title	Description
OG000	PharmaNAC 1800 mg	PharmaNAC 900 mg orally twice daily for 8 weeks 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.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	PharmaNAC 1800 mg	PharmaNAC 900 mg orally twice daily for 8 weeks 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.

ID	Term
D003545	Cysteine
D000603	Amino Acids, Sulfur
D013457	Sulfur Compounds
D009930	Organic Chemicals