Cardiovascular Assessment of the Effects of Tobacco and Nicotine Delivery Products
Condition: Adverse Effect of Other Agents Primarily Affecting the Cardiovascular System, Initial Encounter
Study type: Interventional

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.
    

Intervention name(s): Cigarette, NIDA test type with 16.6 mg nicotine; Cigarette, NIDA test type with <0.45 mg nicotine; Electronic cigarette with 18 mg/ml nicotine; Electronic Cigarette with no nicotine; Moist snuff; Sham Smoking; Secondhand cigarette smoke (SHS); Conditioned, filtered air; Sham Moist Snuff
Intervention type(s): Other; Other; Other; Other; Other; Other; Other; Other; Other
Intervention description(s): Smoke a single cigarette for up to 10 minutes; Smoke a single low-nicotine cigarette for up to 10 minutes; Use electronic cigarette with 18 mg/ml nicotine for 30 minutes; Use electronic cigarette with no nicotine for 30 minutes; Use moist snuff for 30 minutes; Sham smoking or e-cigarette use consists of puffing on a drinking straw for 10 minutes; 180-minute exposure to SHS generated by controlled dilution of smoke from machine-smoked cigarettes; Exposure to conditioned, filtered air for 180 minutes; Chew gum for 30 minutes
Other intervention name(s): Cigarette; Cigarette; commercially available moist oral snuff; Environmental Tobacco Smoke (ETS); ETS; SHS; Clean, filtered, temperature and humidity controlled air; Negative control for SHS exposure; Chewing gum; Negative control for moist oral snuff use
Intervention MeSH terms: Nicotine
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: Cardiovascular; tobacco; cigarettes; secondhand cigarette smoke; SHS; smokeless tobacco; chewing tobacco; snus; electronic cigarettes; vapor; particles; oxidative stress; flow-mediated dilation (FMD); FMD