Clinical trial NCT01964807: Cardiovascular Assessment of the Effects of Tobacco and Nicotine Delivery Products
Official title: Cardiovascular Assessment of the Effects of Tobacco and Nicotine Delivery Products
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Adverse Effect of Other Agents Primarily Affecting the Cardiovascular System, Initial Encounter
Keywords: Cardiovascular
tobacco
cigarettes
secondhand cigarette smoke
SHS
smokeless tobacco
chewing tobacco
snus
electronic cigarettes
vapor
particles
oxidative stress
flow-mediated dilation (FMD)
FMD
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Food and Drug Administration (FDA)
First posted: 2013-10-17
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: The overarching goal of this project is to develop a panel of cardiovascular risk biomarkers that can detect differences in the cardiovascular safety of various tobacco products, whether conventional, new or emerging, in order to help the FDA with the task of regulating them. This will be achieved through 4 aims:

Aim 1: Determine the relative contributions of nicotine and combustion products to the cardiovascular risk of active cigarette smoking.

Aim 2: Determine which cardiovascular risk biomarkers are affected by exposure to secondhand smoke.

Aim 3: Determine the cardiovascular risk of smokeless tobacco use.

Aim 4: Determine the cardiovascular risk of electronic cigarettes and the respective contributions of nicotine and electronic cigarette vapor.

Detailed description: Cigarette smoking is a major cause of cardiovascular disease (CVD).1 In contrast, the cardiovascular risks of other popular tobacco products (smokeless tobacco), new tobacco products ( e-cigarettes) and proposed products (reduced nicotine cigarettes) are not adequately understood. The FDA will need information about the cardiovascular safety of these products to inform their regulatory decisions. While long-term clinical outcome studies of the cardiovascular risks of these tobacco products would be optimal, they take too long to provide the data that the FDA needs now. Disturbances in the function of vascular endothelium (the lining of arteries, which plays an important role in regulating vascular function) and the activation of the autonomic nervous system, as well as increased inflammation, oxidative stress and propensity to thrombosis (clotting), are key mechanisms in the progression of CVD and validated biomarkers of CVD risk. These biomarkers form the basis for our model to assess the CVD risks of tobacco product use and secondhand smoke exposure. We will conduct controlled, short-term exposures of human subjects to test products that provide a wide range of nicotine, particle, and other cardiovascular toxin concentrations to determine how these components associated with tobacco use adversely affect cardiovascular risk.

Eligibility criteria: Inclusion Criteria:

* All Groups: Age 18-50
* Can tolerate withholding their medications for two weeks at a time
* Group 1: Active smokers
* Group 2: Nonsmokers
* Group 3: Active users of smokeless tobacco
* Group 4: Active users of electronic cigarettes
* Additional Inclusion Criteria for E-Cigarette Users:
* Currently use ofe-cigarettes \> 5 times a day
* Has used e-cigarettes for \>3 months
* Additional Inclusion Criteria for Active Smokers: Currently smoke \>5 cigarettes per day ≥ 1 pack year

Exclusion Criteria:

* Exclusion Criteria for all subjects
* Physician diagnosis of:
* asthma
* heart disease
* hypertension
* dyslipidemia
* thyroid disease
* diabetes
* renal or liver impairment
* glaucoma.
* Unstable psychiatric condition (such as current major depression, history of schizophrenia or bipolar disorder)
* current use of more than two psychiatric medications
* Pregnancy or breastfeeding (by history)
* Alcohol, opiate, cocaine, amphetamine or methamphetamine dependence within the past 5 years
* BMI \> 35 and \< 18
* Current opiate, cocaine, amphetamine or methamphetamine use (by history or urine test)
* Occupational exposure to smoke, dusts and fumes
* Concurrent participation in another clinical trial
* Unable to communicate in English
* Additional Exclusion Criteria for Active Smokers:
* Unable to hold marijuana for 1 week prior to each study visit.
* Exhaled carbon monoxide (CO) \<10 ppm at each visit
* Negative salivary cotinine test using a rapid-read, over the counter test with 30 ng/ml cutoff
* Additional Exclusion Criteria for Nonsmokers:
* More than 1 pack year smoking history
* Quit smoking \< 5 years ago
* Ever a daily marijuana smoker
* Smoked anything within the last 3 months
* Additional Inclusion Criteria for Smokeless Tobacco Users:
* Use of moist oral snuff \> 5 times a day
* Has used moist oral snuff for at least 0.5 years
* Additional Exclusion Criteria for Smokeless Tobacco Users:
* Current smoker
* Quit smoking \< 0.5 years ago
* Additional Exclusion Criteria for E-Cigarette Users:
* Current use of other tobacco products
* Unable to hold marijuana for 1 week prior to each study visit

Primary outcomes:
measure: Flow-mediated Dilation of the Brachial Artery
timeFrame: up to 3 hours after use of tobacco product
Secondary outcomes:
measure: Heart Rate Variability (HRV)
timeFrame: up to 3 hours after use of product.
Other outcomes:
measure: Clot strength and plasma levels of interleukin-6 (IL-6) and 8-isoprostane
timeFrame: up to 3 hours after use of product.
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Peter Ganz, M.D.
role: PRINCIPAL_INVESTIGATOR
References: