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Trial record 1 of 1 for:    NCT01964807
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Cardiovascular Assessment of the Effects of Tobacco and Nicotine Delivery Products

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01964807
Recruitment Status : Active, not recruiting
First Posted : October 17, 2013
Last Update Posted : November 17, 2020
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Food and Drug Administration (FDA)
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment Phase
Adverse Effect of Other Agents Primarily Affecting the Cardiovascular System, Initial Encounter Other: Cigarette, NIDA test type with 16.6 mg nicotine Other: Cigarette, NIDA test type with <0.45 mg nicotine Other: Electronic cigarette with 18 mg/ml nicotine Other: Electronic Cigarette with no nicotine Other: Moist snuff Other: Sham Smoking Other: Secondhand cigarette smoke (SHS) Other: Conditioned, filtered air Other: Sham Moist Snuff Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 81 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Cardiovascular Assessment of the Effects of Tobacco and Nicotine Delivery Products
Study Start Date : November 2013
Estimated Primary Completion Date : September 30, 2021
Estimated Study Completion Date : December 30, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cigarette smokers
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.
Other: Cigarette, NIDA test type with 16.6 mg nicotine
Smoke a single cigarette for up to 10 minutes
Other Name: Cigarette

Other: Cigarette, NIDA test type with <0.45 mg nicotine
Smoke a single low-nicotine cigarette for up to 10 minutes
Other Name: Cigarette

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

Experimental: Nonsmokers
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.
Other: Secondhand cigarette smoke (SHS)
180-minute exposure to SHS generated by controlled dilution of smoke from machine-smoked cigarettes
Other Names:
  • Environmental Tobacco Smoke (ETS)
  • ETS
  • SHS

Other: Conditioned, filtered air
Exposure to conditioned, filtered air for 180 minutes
Other Names:
  • Clean, filtered, temperature and humidity controlled air
  • Negative control for SHS exposure

Experimental: Smokeless tobacco users
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.
Other: Moist snuff
Use moist snuff for 30 minutes
Other Name: commercially available moist oral snuff

Other: Sham Moist Snuff
Chew gum for 30 minutes
Other Names:
  • Chewing gum
  • Negative control for moist oral snuff use

Experimental: e-cigarette users
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.
Other: Electronic cigarette with 18 mg/ml nicotine
Use electronic cigarette with 18 mg/ml nicotine for 30 minutes

Other: Electronic Cigarette with no nicotine
Use electronic cigarette with no nicotine for 30 minutes

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




Primary Outcome Measures :
  1. Flow-mediated Dilation of the Brachial Artery [ Time Frame: up to 3 hours after use of tobacco product ]
    Vascular function as measured by Flow-mediated Dilation of the Brachial Artery


Secondary Outcome Measures :
  1. Heart Rate Variability (HRV) [ Time Frame: 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 Outcome Measures:
  1. Clot strength and plasma levels of interleukin-6 (IL-6) and 8-isoprostane [ Time Frame: up to 3 hours after use of product. ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01964807


Locations
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United States, California
University of California, San Francisco
San Francisco, California, United States, 94143
Sponsors and Collaborators
University of California, San Francisco
National Cancer Institute (NCI)
Food and Drug Administration (FDA)
Investigators
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Principal Investigator: Peter Ganz, M.D. University of California, San Francisco
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Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01964807    
Other Study ID Numbers: P0052956
P50CA180890 ( U.S. NIH Grant/Contract )
136316 ( Other Identifier: University of California, San Francisco )
First Posted: October 17, 2013    Key Record Dates
Last Update Posted: November 17, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Information might be disclosed as part of study activities to the FDA

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by University of California, San Francisco:
Cardiovascular
tobacco
cigarettes
secondhand cigarette smoke
SHS
smokeless tobacco
chewing tobacco
snus
electronic cigarettes
vapor
particles
oxidative stress
flow-mediated dilation (FMD)
FMD
Additional relevant MeSH terms:
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Nicotine
Ganglionic Stimulants
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action