Clinical trial NCT00954096: Nicotine Patch, Blood Flow and Oxidative Stress Study
Official title: The Effect Of Nicotine On Indices Of Arterial Function And Oxidative Stress
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
First posted: 2009-08-06
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP

Brief summary: This study will address the hypothesis that nicotine, like cigarette smoking acting as a pro-oxidant may have adverse effects on arterial function.

Detailed description: Smoking causes \>400,000 deaths from cardiovascular disease (CVD) per year. The molecular basis of smoking induced tissue injury remains unclear but considerable evidence supports a role for oxidant stress (OS).

Arterial function has been shown to be impaired in smokers even before the onset of angiographically demonstrable atherosclerosis. Defects in endothelium dependant flow mediated vasodilatation (FMD) are seen in those at risk of or with overt vascular disease.

Cigarette smoking is highly addictive. Spontaneous quit rates approximate 3%. Even those using nicotine replacement therapy (NRT) have high relapse rates (67-75%) on completion of the 8-12 week course of NRT. Thus there is interest in the use of extended NRT as a "safer" alternative to cigarette smoking. However such assumptions may be premature. Nicotine demonstrates proxidant effects in vitro and in small studies has been associated with endothelial dysfunction. Studies simultaneously assessing the effects of nicotine on oxidative stress and arterial function in humans have not been performed.

The current proposal will address the hypothesis that nicotine, like cigarette smoking acting as a pro-oxidant may have adverse effects on arterial function.

Eligibility criteria: Inclusion Criteria:

* Healthy individuals
* Nonsmokers who have never smoked
* Normal medical history
* Normal physical examination
* Normal laboratory data
* Negative urinary pregnancy test for females

Exclusion Criteria:

* Previous CVD
* Chronic medication use
* History alcoholism
* History of smoking
* Current pregnancy
* Subjects, who have less than or equal to 60% platelet aggregation in response to arachidonic acid will also be excluded.

Primary outcomes:
measure: Assess the dose-related effects of nicotine in humans, on novel indices of lipid peroxidation, protein oxidation and DNA modification by lipid adducts.
timeFrame: 1 - 3 years
Secondary outcomes:
measure: Assess the dose-related effects of nicotine in humans on COX activation.
timeFrame: 1 year
measure: Assess the dose-related effects of nicotine in humans on blood flow mediated arterial function.
timeFrame: 3 - 6 months
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania Institute for Translational Medicine and Therapeutics
name: Garret A FitzGerald, MD
role: PRINCIPAL_INVESTIGATOR
References: