Adverse Effect of Other Agents Primarily Affecting the Cardiovascular System, Initial EncounterNCT01964807
Cardiovascular Assessment of the Effects of Tobacco and Nicotine Delivery Products
A study testing Cigarette, NIDA test type with 16.6 mg nicotine, Cigarette, NIDA test type with <0.45 mg nicotine and Electronic cigarette with 18 mg/ml nicotine in people with Adverse Effect of Other Agents Primarily Affecting the Cardiovascular System, Initial Encounter, run by University of California, San Francisco at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Adverse Effect of Other Agents Primarily Affecting the Cardiovascular System, Initial Encounter
- What is being tested?
- Cigarette, NIDA test type with 16.6 mg nicotine, Cigarette, NIDA test type with <0.45 mg nicotine and Electronic cigarette with 18 mg/ml nicotine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 81 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Nov 2013to 31 May 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Show all 10Show fewer
- 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
Who cannot join
- Physician diagnosis of:
- asthma
- heart disease
- hypertension
- dyslipidemia
- thyroid disease
Show all 36Show fewer
- 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 locations and contacts
1 site in 1 country.
United States1 site
University of California, San Francisco
San Francisco, California, 94143
About this study
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.
Read more
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.
Read the 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.
- Conditions
- Adverse Effect of Other Agents Primarily Affecting the Cardiovascular System, Initial Encounter
- Being tested
- 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
- Keywords
- Cardiovascular, tobacco, cigarettes, secondhand cigarette smoke, SHS, smokeless tobacco, chewing tobacco, snus, electronic cigarettes, vapor, particles, oxidative stress, flow-mediated dilation (FMD), FMD
- Medical subject headings
- Tobacco Use, Vaping
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cigarette, NIDA test type with 16.6 mg nicotineOther
Also called Cigarette
Smoke a single cigarette for up to 10 minutes
Cigarette, NIDA test type with <0.45 mg nicotineOther
Also called Cigarette
Smoke a single low-nicotine cigarette for up to 10 minutes
Electronic cigarette with 18 mg/ml nicotineOther
Use electronic cigarette with 18 mg/ml nicotine for 30 minutes
Electronic Cigarette with no nicotineOther
Use electronic cigarette with no nicotine for 30 minutes
Moist snuffOther
Also called commercially available moist oral snuff
Use moist snuff for 30 minutes
Sham SmokingOther
Sham smoking or e-cigarette use consists of puffing on a drinking straw for 10 minutes
Secondhand cigarette smoke (SHS)Other
Also called Environmental Tobacco Smoke (ETS), ETS, SHS
180-minute exposure to SHS generated by controlled dilution of smoke from machine-smoked cigarettes
Conditioned, filtered airOther
Also called Clean, filtered, temperature and humidity controlled air, Negative control for SHS exposure
Exposure to conditioned, filtered air for 180 minutes
Sham Moist SnuffOther
Also called Chewing gum, Negative control for moist oral snuff use
Chew gum for 30 minutes
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Cigarette, NIDA test type with 16.6 mg nicotine; Other: Cigarette, NIDA test type with <0.45 mg nicotine; Other: Sham Smoking |
| 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. Receives: Other: Secondhand cigarette smoke (SHS); Other: Conditioned, filtered air |
| 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. Receives: Other: Moist snuff; Other: Sham Moist Snuff |
| 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. Receives: Other: Electronic cigarette with 18 mg/ml nicotine; Other: Electronic Cigarette with no nicotine; Other: Sham Smoking |
What is being measured
The primary outcome is the main question the study is designed to answer.
Flow-mediated Dilation of the Brachial Artery
Vascular function as measured by Flow-mediated Dilation of the Brachial Artery
Measured: up to 3 hours after use of tobacco product
Secondary outcomes (1)
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
Measured: up to 3 hours after use of product.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2013 (estimated)
- Study start3 Nov 2013
- Primary completion31 May 2021
- Study completion31 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adverse Effect of Other Agents Primarily Affecting the Cardiovascular System, Initial EncounterStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Food and Drug Administration (FDA)
- Responsible party
- Sponsor
- Investigators
- Peter Ganz, M.D., Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01964807
- Sponsor's protocol ID
- P0052956
- Other IDs
- P50CA180890, 136316
- Status last verified
- Dec 2021
- First submitted
- 4 Oct 2013
- Last updated
- 27 Dec 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Information might be disclosed as part of study activities to the FDA
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cardiovascular Assessment of the Effects of Tobacco and Nicotine Delivery Products
- ClinicalTrials.gov ID
- NCT01964807
- Acronym / sponsor ID
- P0052956
- Conditions
- Adverse Effect of Other Agents Primarily Affecting the Cardiovascular System, Initial Encounter
- Keywords
- Cardiovascular, tobacco, cigarettes, secondhand cigarette smoke, SHS, smokeless tobacco, chewing tobacco, snus
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 81 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Food and Drug Administration (FDA)
- Study start
- 3 Nov 2013 (actual)
- Primary completion
- 31 May 2021 (actual)
- Study completion
- 31 May 2021 (actual)
- First posted
- 17 Oct 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cigarette smokers | Experimental | Other: Cigarette, NIDA test type with 16.6 mg nicotine, Other: Cigarette, NIDA test type with <0.45 mg nicotine, Other: Sham 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. |
| Nonsmokers | Experimental | Other: Secondhand cigarette smoke (SHS), Other: Conditioned, 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 users | Experimental | Other: Moist snuff, Other: Sham 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. |
| e-cigarette users | Experimental | Other: Electronic cigarette with 18 mg/ml nicotine, Other: Electronic Cigarette with no nicotine, Other: Sham 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. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (36 listed)
- Physician diagnosis of:
- asthma
- heart disease
- hypertension
- dyslipidemia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cigarette, NIDA test type with 16.6 mg nicotineAlso: CigaretteSmoke a single cigarette for up to 10 minutes | Other | Cigarette smokers |
| Cigarette, NIDA test type with <0.45 mg nicotineAlso: CigaretteSmoke a single low-nicotine cigarette for up to 10 minutes | Other | Cigarette smokers |
| Electronic cigarette with 18 mg/ml nicotineUse electronic cigarette with 18 mg/ml nicotine for 30 minutes | Other | e-cigarette users |
| Electronic Cigarette with no nicotineUse electronic cigarette with no nicotine for 30 minutes | Other | e-cigarette users |
| Moist snuffAlso: commercially available moist oral snuffUse moist snuff for 30 minutes | Other | Smokeless tobacco users |
| Sham SmokingSham smoking or e-cigarette use consists of puffing on a drinking straw for 10 minutes | Other | Cigarette smokers, e-cigarette users |
| Secondhand cigarette smoke (SHS)Also: Environmental Tobacco Smoke (ETS), ETS, SHS180-minute exposure to SHS generated by controlled dilution of smoke from machine-smoked cigarettes | Other | Nonsmokers |
| Conditioned, filtered airAlso: Clean, filtered, temperature and humidity controlled air, Negative control for SHS exposureExposure to conditioned, filtered air for 180 minutes | Other | Nonsmokers |
| Sham Moist SnuffAlso: Chewing gum, Negative control for moist oral snuff useChew gum for 30 minutes | Other | Smokeless tobacco users |
Primary outcome
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
1 secondary outcome
Heart Rate Variability (HRV)
Time frame: up to 3 hours after use of product.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2021.
- Individual participant dataSharing planned: Yes. Information might be disclosed as part of study activities to the FDA
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Ganz, M.D. principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cigarette, NIDA test type with 16.6 mg nicotine, Cigarette, NIDA test type with <0.45 mg nicotine and Electronic cigarette with 18 mg/ml nicotine in people with Adverse Effect of Other Agents Primarily Affecting the Cardiovascular System, Initial Encounter, run by University of California, San Francisco at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Flow-mediated Dilation of the Brachial Artery (time frame: up to 3 hours after use of tobacco product). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Dec 2021.