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| ID | Type | Description | Link |
|---|---|---|---|
| P50CA180890 | U.S. NIH Grant/Contract | View source | |
| 136316 | Other Identifier | University of California, San Francisco |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
| Food and Drug Administration (FDA) | FED |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cigarette smokers | Experimental | 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. |
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| Nonsmokers | Experimental | 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. |
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| Smokeless tobacco users | Experimental | 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. |
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| e-cigarette users | Experimental | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cigarette, NIDA test type with 16.6 mg nicotine | Other | Smoke a single cigarette for up to 10 minutes |
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| Measure | Description | Time Frame |
|---|---|---|
| Flow-mediated Dilation of the Brachial Artery | Vascular function as measured by Flow-mediated Dilation of the Brachial Artery | up to 3 hours after use of tobacco product |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | up to 3 hours after use of product. |
| Measure | Description | Time Frame |
|---|---|---|
| Clot strength and plasma levels of interleukin-6 (IL-6) and 8-isoprostane | up to 3 hours after use of product. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Peter Ganz, M.D. | University of California, San Francisco | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, San Francisco | San Francisco | California | 94143 | United States |
Information might be disclosed as part of study activities to the FDA
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| Cigarette, NIDA test type with <0.45 mg nicotine | Other | Smoke a single low-nicotine cigarette for up to 10 minutes |
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| Electronic cigarette with 18 mg/ml nicotine | Other | Use electronic cigarette with 18 mg/ml nicotine for 30 minutes |
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| Electronic Cigarette with no nicotine | Other | Use electronic cigarette with no nicotine for 30 minutes |
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| Moist snuff | Other | Use moist snuff for 30 minutes |
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| Sham Smoking | Other | Sham smoking or e-cigarette use consists of puffing on a drinking straw for 10 minutes |
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| Secondhand cigarette smoke (SHS) | Other | 180-minute exposure to SHS generated by controlled dilution of smoke from machine-smoked cigarettes |
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| Conditioned, filtered air | Other | Exposure to conditioned, filtered air for 180 minutes |
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| Sham Moist Snuff | Other | Chew gum for 30 minutes |
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| ID | Term |
|---|---|
| D064424 | Tobacco Use |
| D000072137 | Vaping |
| ID | Term |
|---|---|
| D001519 | Behavior |
| D012907 | Smoking |
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| ID | Term |
|---|---|
| D062789 | Tobacco Products |
| D009538 | Nicotine |
| D066300 | Electronic Nicotine Delivery Systems |
| D014028 | Tobacco Smoke Pollution |
| D013696 | Temperature |
| D002638 | Chewing Gum |
| ID | Term |
|---|---|
| D000074602 | Smoking Devices |
| D008420 | Manufactured Materials |
| D013676 | Technology, Industry, and Agriculture |
| D012991 | Solanaceous Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D012906 | Smoke |
| D052638 | Particulate Matter |
| D045424 | Complex Mixtures |
| D000397 | Air Pollution |
| D004787 | Environmental Pollution |
| D011634 | Public Health |
| D004778 | Environment and Public Health |
| D013816 | Thermodynamics |
| D055585 | Physical Phenomena |
| D014887 | Weather |
| D001272 | Atmosphere |
| D004777 | Environment |
| D055669 | Ecological and Environmental Phenomena |
| D001686 | Biological Phenomena |
| D008685 | Meteorological Concepts |
| D004780 | Environment, Controlled |
| D053149 | Plant Gums |
| D001704 | Biopolymers |
| D011108 | Polymers |
| D046911 | Macromolecular Substances |
| D011134 | Polysaccharides |
| D002241 | Carbohydrates |
| D053147 | Plant Exudates |
| D001688 | Biological Products |
| D002182 | Candy |
| D005502 | Food |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |
| D019602 | Food and Beverages |
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