Nicotine Patch, Blood Flow and Oxidative Stress Study

• ClinicalTrials.gov Identifier: NCT00954096
• Recruitment Status: Completed
• First Posted: August 6, 2009
• Last Update Posted: October 27, 2009
• Sponsor: University of Pennsylvania
• Collaborator: National Institutes of Health (NIH)
• Information provided by: University of Pennsylvania

Tracking Information

• First Submitted Date: July 29, 2009
• First Posted Date: August 6, 2009
• Last Update Posted Date: October 27, 2009
• Study Start Date: October 2002
• Actual Primary Completion Date: November 2006 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: August 5, 2009): Assess the dose-related effects of nicotine in humans, on novel indices of lipid peroxidation, protein oxidation and DNA modification by lipid adducts. [ Time Frame: 1 - 3 years ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 5, 2009)

• Assess the dose-related effects of nicotine in humans on COX activation. [ Time Frame: 1 year ]
• Assess the dose-related effects of nicotine in humans on blood flow mediated arterial function. [ Time Frame: 3 - 6 months ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Nicotine Patch, Blood Flow and Oxidative Stress Study
• Official Title: The Effect Of Nicotine On Indices Of Arterial Function And Oxidative Stress
• 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.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: Double (Participant, Investigator)
• Condition: Healthy

Intervention

Drug: transdermal nicotine patch (7mg)

A 7mg transdermal nicotine patch will be applied to the subject's arm for an 8 hour period.

Other Names:

• Nicotine patch
• Habitrol
• Nicoderm CQ
• Nicotrol

Study Arms

Experimental: Transdermal nicotine patch or placebo

A single blood specimen (85ml) will be drawn. They will be asked to empty their bladder. The patch will be applied. Following application of the patch, heart rate and blood pressure will be measured every 15 minutes for the 1st hour, every 30 minutes for the next 3 hours and hourly after that until the end of the study. Urine will be collected in two 4-hour aliquots. FMD will be measured after approximately 6 hours of nicotine exposure. After 8 hours exposure, following the end of the 2nd urine collection, the patch will be removed and the subject discharged. Following a minimum of 2 weeks (maximum 8 weeks) washout, the subject will repeat the study, receiving the other patch.

Intervention: Drug: transdermal nicotine patch (7mg)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 5, 2009): 55
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: December 2006
• Actual Primary Completion Date: November 2006 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 45 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00954096
• Other Study ID Numbers: 707275; 0875
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Garret A. FitzGerald M.D Chair, Department of Pharmacology- Director, Institute for Translational Medicine and Therapeutics, University of Pennsylvania
• Study Sponsor: University of Pennsylvania
• Collaborators: National Institutes of Health (NIH)

Investigators

• Principal Investigator: Garret A FitzGerald, MD; University of Pennsylvania Institute for Translational Medicine and Therapeutics

• PRS Account: University of Pennsylvania
• Verification Date: October 2009