Cardiovascular Assessment of the Effects of Tobacco and Nicotine Delivery Products

N/ACompletedNCT01964807

University of California, San Francisco81 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

OTHER

Interventions

Cigarette, NIDA test type with 16.6 mg nicotineOTHER

Smoke a single cigarette for up to 10 minutes

Cigarette, NIDA test type with <0.45 mg nicotineOTHER

Smoke a single low-nicotine cigarette for up to 10 minutes

Electronic cigarette with 18 mg/ml nicotineOTHER

Use electronic cigarette with 18 mg/ml nicotine for 30 minutes

Electronic Cigarette with no nicotineOTHER

Use electronic cigarette with no nicotine for 30 minutes

Moist snuffOTHER

Use moist snuff for 30 minutes

Sham SmokingOTHER

Sham smoking or e-cigarette use consists of puffing on a drinking straw for 10 minutes

Secondhand cigarette smoke (SHS)OTHER

180-minute exposure to SHS generated by controlled dilution of smoke from machine-smoked cigarettes

Conditioned, filtered airOTHER

Exposure to conditioned, filtered air for 180 minutes

Sham Moist SnuffOTHER

Chew gum for 30 minutes

Eligibility

Sex: ALLMin age: 18 YearsMax age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Flow-mediated Dilation of the Brachial Artery

Vascular function as measured by Flow-mediated Dilation of the Brachial Artery

Time frame: up to 3 hours after use of tobacco product

Secondary Outcomes

Heart Rate Variability (HRV)

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

Time frame: up to 3 hours after use of product.