Cardiovascular Assessment of the Effects of Tobacco and Nicotine Delivery Products

University of California San Francisco (UCSF)

Status: Completed

Conditions: Adverse Effect of Other Agents Primarily Affecting the Cardiovascular System, Initial Encounter

Treatments: Other: Conditioned, filtered air; Other: Electronic Cigarette with no nicotine; Other: Cigarette, NIDA test type with 16.6 mg nicotine; Other: Sham Moist Snuff; Other: Cigarette, NIDA test type with <0.45 mg nicotine; Other: Moist snuff; Other: Electronic cigarette with 18 mg/ml nicotine; Other: Sham Smoking; Other: Secondhand cigarette smoke (SHS)

Study type: Interventional

Funder types: Other; Other U.S. Federal agency; NIH

Identifiers

NCT01964807

P0052956

P50CA180890 (U.S. NIH Grant/Contract)

136316 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 81 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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81 participants in 4 patient groups

Cigarette smokers

Experimental group

Description:

Will 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.

Treatment:

Other: Sham Smoking

Other: Cigarette, NIDA test type with <0.45 mg nicotine

Other: Cigarette, NIDA test type with 16.6 mg nicotine

Nonsmokers

Experimental group

Description:

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.

Treatment:

Other: Secondhand cigarette smoke (SHS)

Other: Conditioned, filtered air

Smokeless tobacco users

Experimental group

Description:

Will 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.

Treatment:

Other: Moist snuff

Other: Sham Moist Snuff

e-cigarette users

Experimental group

Description:

Will 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.

Treatment:

Other: Electronic Cigarette with no nicotine

Other: Electronic cigarette with 18 mg/ml nicotine

Other: Sham Smoking