Adverse Effect of Other Agents Primarily Affecting the Cardiovascular System, Initial Encounter
Conditions
Keywords
Cardiovascular, tobacco, cigarettes, secondhand cigarette smoke, SHS, smokeless tobacco, chewing tobacco, snus, electronic cigarettes, vapor, particles, oxidative stress, flow-mediated dilation (FMD), FMD
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.
Interventions
OTHERCigarette, NIDA test type with 16.6 mg nicotine
Smoke a single cigarette for up to 10 minutes
OTHERCigarette, NIDA test type with <0.45 mg nicotine
Smoke a single low-nicotine cigarette for up to 10 minutes
OTHERElectronic cigarette with 18 mg/ml nicotine
Use electronic cigarette with 18 mg/ml nicotine for 30 minutes
OTHERElectronic Cigarette with no nicotine
Use electronic cigarette with no nicotine for 30 minutes
OTHERMoist snuff
Use moist snuff for 30 minutes
OTHERSham Smoking
Sham smoking or e-cigarette use consists of puffing on a drinking straw for 10 minutes
OTHERSecondhand cigarette smoke (SHS)
180-minute exposure to SHS generated by controlled dilution of smoke from machine-smoked cigarettes
OTHERConditioned, filtered air
Exposure to conditioned, filtered air for 180 minutes
OTHERSham Moist Snuff
Chew gum for 30 minutes
Sponsors
National Cancer Institute (NCI)
Food and Drug Administration (FDA)
University of California, San Francisco
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
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
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Flow-mediated Dilation of the Brachial Artery | up to 3 hours after use of tobacco product | Vascular function as measured by Flow-mediated Dilation of the Brachial Artery |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Heart Rate Variability (HRV) | up to 3 hours after use of product. | HRV refers to variation in the intervals between consecutive heart beats. Low HRV predicts poor prognosis and increased mortality in patients with cardiovascular disease and in apparently healthy subjects |
Other
| Measure | Time frame |
|---|---|
| Clot strength and plasma levels of interleukin-6 (IL-6) and 8-isoprostane | up to 3 hours after use of product. |
Countries
United States
Outcome results
None listed