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Cardiovascular Assessment of the Effects of Tobacco and Nicotine Delivery Products

Not Applicable
Completed
Conditions
Adverse Effect of Other Agents Primarily Affecting the Cardiovascular System, Initial Encounter
Interventions
Other: Electronic cigarette with 18 mg/ml nicotine
Other: Cigarette, NIDA test type with 16.6 mg nicotine
Other: Secondhand cigarette smoke (SHS)
Other: Moist snuff
Other: Electronic Cigarette with no nicotine
Other: Cigarette, NIDA test type with <0.45 mg nicotine
Other: Conditioned, filtered air
Other: Sham Moist Snuff
Other: Sham Smoking
Registration Number
NCT01964807
Lead Sponsor
University of California, San Francisco
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
81
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
Read More
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
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Cigarette smokersSham SmokingWill smoke 1 cigarette, National Institute of Drug Abuse (NIDA) test type with 16.6 mg nicotine; 1 cigarette, NIDA test type with \<0.45 mg nicotine; perform sham smoking by puffing on a drinking straw. Each intervention will last 10 minutes, and each will take place one time, on one of 3 study visits, in random order.
e-cigarette usersElectronic Cigarette with no nicotineWill use one electronic cigarette with 18 mg/ml nicotine, one electronic cigarette with no nicotine, and will perform sham smoking by puffing on a drinking straw. Each intervention will last 10 minutes, and each will take place one time, on one of 3 study visits, in random order.
Cigarette smokersCigarette, NIDA test type with <0.45 mg nicotineWill smoke 1 cigarette, National Institute of Drug Abuse (NIDA) test type with 16.6 mg nicotine; 1 cigarette, NIDA test type with \<0.45 mg nicotine; perform sham smoking by puffing on a drinking straw. Each intervention will last 10 minutes, and each will take place one time, on one of 3 study visits, in random order.
e-cigarette usersElectronic cigarette with 18 mg/ml nicotineWill use one electronic cigarette with 18 mg/ml nicotine, one electronic cigarette with no nicotine, and will perform sham smoking by puffing on a drinking straw. Each intervention will last 10 minutes, and each will take place one time, on one of 3 study visits, in random order.
Cigarette smokersCigarette, NIDA test type with 16.6 mg nicotineWill smoke 1 cigarette, National Institute of Drug Abuse (NIDA) test type with 16.6 mg nicotine; 1 cigarette, NIDA test type with \<0.45 mg nicotine; perform sham smoking by puffing on a drinking straw. Each intervention will last 10 minutes, and each will take place one time, on one of 3 study visits, in random order.
NonsmokersSecondhand cigarette smoke (SHS)Will undergo secondhand cigarette smoke (SHS) exposure and conditioned, filtered air exposure. Each intervention will last 180 minutes, and each will take place one time, on one of 2 study visits, in random order.
Smokeless tobacco usersMoist snuffWill use 1 pouch of commercially available moist oral snuff and will chew gum (sham moist snuff). Each intervention will last 30 minutes, and each will take place one time, on one of 2 study visits, in random order.
e-cigarette usersSham SmokingWill use one electronic cigarette with 18 mg/ml nicotine, one electronic cigarette with no nicotine, and will perform sham smoking by puffing on a drinking straw. Each intervention will last 10 minutes, and each will take place one time, on one of 3 study visits, in random order.
NonsmokersConditioned, filtered airWill undergo secondhand cigarette smoke (SHS) exposure and conditioned, filtered air exposure. Each intervention will last 180 minutes, and each will take place one time, on one of 2 study visits, in random order.
Smokeless tobacco usersSham Moist SnuffWill use 1 pouch of commercially available moist oral snuff and will chew gum (sham moist snuff). Each intervention will last 30 minutes, and each will take place one time, on one of 2 study visits, in random order.
Primary Outcome Measures
NameTimeMethod
Flow-mediated Dilation of the Brachial Arteryup to 3 hours after use of tobacco product

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

Secondary Outcome Measures
NameTimeMethod
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

Trial Locations

Locations (1)

University of California, San Francisco

🇺🇸

San Francisco, California, United States

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