Nicotine DependenceNCT02470754
Clinical Pharmacology of Electronic Cigarettes
A study testing Tobacco Cigarette and Electronic Cigarette in people with Nicotine Dependence, run by University of California, San Francisco at 2 sites in United States.
Trial summary
The purpose of this study is to learn more about nicotine exposure and the safety of electronic cigarettes (EC). It will focus on the areas that are thought to most closely relate to the addictive potential of EC, namely: (1) EC as nicotine delivery devices, covering issues of nicotine intake and pharmacokinetics… Read more about this study
- Who is it for?
- Ages 21 years and olderHealthy volunteers can take part
- Conditions the study is for
- Nicotine Dependence
- What is being tested?
- Tobacco Cigarette and Electronic Cigarette
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 2 sitesUnited States
- Study dates
- 23 Jul 2015to 2 Feb 2018
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 21 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy on the basis of medical history and limited physical examination as described below:
- Heart rate < 105 BPM*
- Systolic Blood Pressure < 160 and > 90*
- Diastolic Blood Pressure < 100 and > 50*
- Body Mass Index ≤ 38.0 *Considered out of range if both machine and manual readings are above/below these thresholds.
- Current regular "dual" user of both EC and conventional TC
Show all 10Show fewer
- EC device is one of the most popular 1st, 2nd or 3rd generation brands (with the exception of rebuildable atomizers) as determined at time of study commencement
- Carbon monoxide ≥ 5 ppm or per discretion of Principal Investigator
- Saliva cotinine ≥50 ng/ml or urine cotinine
- Age: ≥ 21 years
Who cannot join
- Current regular use of selected psychiatric medications
- Current regular use of cardiovascular medications for cardiovascular conditions including hypertension (Example: beta and alpha-blockers)
- Current regular use of medications inducers of nicotine metabolizing enzymes CYP2A6 (Example: rifampicin, dexamethasone, phenobarbital, and other anticonvulsant drugs).
- Use of other tobacco products
- Pregnancy or breastfeeding (by history and pregnancy test)
- Concurrent use of nicotine-containing medications
Show all 11Show fewer
- Drug/Alcohol Dependence
- Positive toxicology test at the screening visit (THC okay)
- Concurrent participation in another clinical trial
- Inability to communicate in English
- Planning to quit smoking within the next 60 days
Trial locations and contacts
2 sites in 1 country.
United States2 sites
San Francisco General Hospital (SFGH)
San Francisco, California, 94110
University of California, San Francisco (UCSF)
San Francisco, California, 94110
About this study
The purpose of this study is to learn more about nicotine exposure and the safety of electronic cigarettes (EC). It will focus on the areas that are thought to most closely relate to the addictive potential of EC, namely: (1) EC as nicotine delivery devices, covering issues of nicotine intake and pharmacokinetics, temporal patterns of use and titration of nicotine; and (2) subjective effects of EC use, including relationship of use to reward, withdrawal and craving.
Read the detailed description
Electronic cigarettes (EC) are nicotine delivery devices that generate a nicotine-containing aerosol which is inhaled by the user. EC are perceived by users to be useful in helping quitting smoking of conventional tobacco cigarettes (TC) as well as having a presumed lower risk of adverse health effects compared to TC, the potential for use in public places, reduced cost, and lack of the noxious clinging odors associated with TC use. Many believe that electronic cigarette (EC) function as nicotine delivery devices in the same way as tobacco cigarettes (TC), and that EC will prove to be just as addictive as TC, but this may not be the case because of fundamental differences in the design and method of use of these products. Investigators hypothesize that systemic nicotine exposure will be lower with EC compared to TC; that despite lower nicotine intake EC users will experience similar reward and no greater withdrawal symptoms or craving compared to TC; and that dual EC/ TC users will not titrate their daily intake of nicotine in the same way that TC smokers of high- vs low-yield nicotine TC do.
Investigators specifically focus on the areas that are thought to most closely relate to the addictive potential of EC, namely: (1) EC as nicotine delivery devices, covering issues of nicotine intake and pharmacokinetics, temporal patterns of use and titration of nicotine; and (2) subjective effects of EC use, including relationship of use to reward, withdrawal and craving. The investigators will also examine aspects of safety of EC use (by assessment of cardiovascular and hormonal effects of use and of biomarkers of exposure to potentially toxic constituents) and explore the identification and validation of biomarkers that may be useful in distinguishing EC from TC use. Study subjects will be dual users of TC and EC so that the investigators may compare both modalities of use in experienced users in a within-subject design.
The study will consist of two 1-week blocks (EC-only or TC-only conditions) with 4 days of outpatient ad libitum product use followed by 3 days in a clinical research ward to include a single-use pharmacokinetic study, monitoring of product use, subjective assessments, blood and urine collections to assess biomarkers, and a 24-hour period of cardiovascular monitoring. Two additional days at the end of the 2nd block will assess similar measurements during a period of nicotine-product abstention.
- Conditions
- Nicotine Dependence
- Being tested
- Tobacco Cigarette, Electronic Cigarette
- Medical subject headings
- Tobacco Use Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tobacco CigaretteDevice
Also called TC, Cigarette
Usual brand tobacco cigarette smoked by study participant.
Electronic CigaretteDevice
Also called EC, E-cig, E-cigarette
Usual brand electronic cigarettes smoked by study participant.
| Study group | Role | What they receive |
|---|---|---|
| EC Block1/TC Block 2 | Active comparator | Participants will be randomized into one of two groups. In this group, participants will be assigned to Electronic Cigarettes only for Study Block #1, then crossover to Tobacco Cigarettes only for Study Block #2. Receives: Device: Tobacco Cigarette; Device: Electronic Cigarette |
| TC Block 1/EC Block 2 | Active comparator | Participants will be randomized into one of two groups. In this group, participants will be assigned to Tobacco Cigarettes only for Study Block #1, then crossover to Electronic Cigarettes only for Study Block #2. Receives: Device: Tobacco Cigarette; Device: Electronic Cigarette |
What is being measured
The primary outcome is the main question the study is designed to answer.
Standardized Session: Mean CMax
Maximum Plasma Nicotine Concentration (Cmax) (ng/mL)
Measured: Inpatient Day 1, Up to 4 Hours post Nicotine Administration
Standardized Session: Mean TMax
Time (min) when Max Plasma Nicotine Concentration was achieved
Measured: Inpatient Day 1, Up to 4 Hours post Session
Standardized Session: AUC 0-240
Plasma Nicotine area-under-the curve from 0 to 4 Hours (min*ng/ml)
Measured: Inpatient Day 1, Up to 4 Hours post Session
PK-estimated Nicotine Dose
Estimated in dose received (in milligrams) during the Standardized Session.
Measured: Inpatient Day 1, Up to 4 Hours post Session
Secondary outcomes (6)
Standardized Session: QSU Factor 1 (Vaping)
Questionnaire for Smoking Urges Brief modified for e-cigarettes to measure urge to vape.Two factor scores and a total score were derived. Factor 1 represents the desire and intention to smoke with smoking perceived as rewarding, while Factor 2 represents an anticipation of relief from negative effect with an urgent desire to smoke.Scores range from 5 to 35 with higher scores indicating a higher level of craving.
Measured: Inpatient Day 1, Up to 4 Hours post Session
Standardized Session: Positive and Negative Affect Score (Negative Affect)
The PANAS Scale or Positive and Negative Affect Schedule (PANAS) is a self-report questionnaire. PANAS, (Sandín et al., 1999; Watson, Clark \& Tellegen, 1988).This instrument is composed of 20 items: 10 items measuring positive affective states and 10 items measuring negative affect states.This subscale measures a person's negative emotions. Scores range from 10- 50 with higher scores indicating stronger negative feelings.
Measured: Inpatient Day 1, Up to 4 Hours post Session
Standardized Session: Minnesota Nicotine Withdrawal Scale
Minnesota Nicotine Withdrawal Scale (MNWS) is a Self-Report Scale for measuring the severity of nicotine withdrawal symptoms.The possible range of scores for the 12-Item MNWS is between 0 and 48 with higher scores indicated greater withdrawal symptom severity.
Measured: Inpatient Day 1, Up to 4 Hours post Session
Standardized Session: QSU Factor 2 (Vaping)
Questionnaire for Smoking Urges Brief modified for e-cigarettes to measure urge to vape.Two factor scores and a total score were derived. Factor 1 represents the desire and intention to smoke with smoking perceived as rewarding, while Factor 2 represents an anticipation of relief from negative effect with an urgent desire to smoke. Scores range from 5 to 35 with higher scores indicating a higher level of craving.
Measured: Inpatient Day 1, Up to 4 Hours post Session
Standardized Session: QSU Factor 1 (Smoking)
Questionnaire for Smoking Urges Brief measures urge to smoke.Two factor scores and a total score were derived. Factor 1 represents the desire and intention to smoke with smoking perceived as rewarding, while Factor 2 represents an anticipation of relief from negative effect with an urgent desire to smoke. Scores range from 5 to 35 with higher scores indicating a higher level of craving.
Measured: Inpatient Day 1, Up to 4 Hours post Session
Standardized Session: QSU Factor 2 (Smoking)
Questionnaire for Smoking Urges Brief measures urge to smoke.Two factor scores and a total score were derived. Factor 1 represents the desire and intention to smoke with smoking perceived as rewarding, while Factor 2 represents an anticipation of relief from negative effect with an urgent desire to smoke. Scores range from 5 to 35 with higher scores indicating a higher level of craving.
Measured: Inpatient Day 1, Up to 4 Hours post Session
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2015 (estimated)
- Study start23 Jul 2015
- Primary completion2 Feb 2018
- Study completion2 Feb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Nicotine DependenceStudies 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), Roswell Park Cancer Institute, National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Neal L Benowitz, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02470754
- Sponsor's protocol ID
- 15635
- Other IDs
- R01DA039264, NCI-2018-02897
- Status last verified
- Jun 2023
- First submitted
- 30 Apr 2015
- Last updated
- 22 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Benowitz NL, St Helen G, Nardone N, Addo N, Zhang JJ, Harvanko AM, Calfee CS, Jacob P 3rd. Twenty-Four-Hour Cardiovascular Effects of Electronic Cigarettes Compared With Cigarette Smoking in Dual Users. J Am Heart Assoc. 2020 Dec;9(23):e017317. doi: 10.1161/JAHA.120.017317. Epub 2020 Nov 19.
PubMed 33208019
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Pharmacology of Electronic Cigarettes
- ClinicalTrials.gov ID
- NCT02470754
- Acronym / sponsor ID
- 15635
- Conditions
- Nicotine Dependence
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), Roswell Park Cancer Institute, National Institute on Drug Abuse (NIDA)
- Study start
- 23 Jul 2015 (actual)
- Primary completion
- 2 Feb 2018 (actual)
- Study completion
- 2 Feb 2018 (actual)
- First posted
- 12 Jun 2015 (estimated)
- Results
- Posted 13 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to learn more about nicotine exposure and the safety of electronic cigarettes (EC). It will focus on the areas that are thought to most closely relate to the addictive potential of EC, namely: (1) EC as nicotine delivery devices, covering issues of nicotine intake and pharmacokinetics, temporal patterns of use and titration of nicotine; and (2) subjective effects of EC use, including relationship of use to reward, withdrawal and craving.
Detailed description
Electronic cigarettes (EC) are nicotine delivery devices that generate a nicotine-containing aerosol which is inhaled by the user. EC are perceived by users to be useful in helping quitting smoking of conventional tobacco cigarettes (TC) as well as having a presumed lower risk of adverse health effects compared to TC, the potential for use in public places, reduced cost, and lack of the noxious clinging odors associated with TC use. Many believe that electronic cigarette (EC) function as nicotine delivery devices in the same way as tobacco cigarettes (TC), and that EC will prove to be just as addictive as TC, but this may not be the case because of fundamental differences in the design and method of use of these products. Investigators hypothesize that systemic nicotine exposure will be lower with EC compared to TC; that despite lower nicotine intake EC users will experience similar reward and no greater withdrawal symptoms or craving compared to TC; and that dual EC/ TC users will not titrate their daily intake of nicotine in the same way that TC smokers of high- vs low-yield nicotine TC do.
Investigators specifically focus on the areas that are thought to most closely relate to the addictive potential of EC, namely: (1) EC as nicotine delivery devices, covering issues of nicotine intake and pharmacokinetics, temporal patterns of use and titration of nicotine; and (2) subjective effects of EC use, including relationship of use to reward, withdrawal and craving. The investigators will also examine aspects of safety of EC use (by assessment of cardiovascular and hormonal effects of use and of biomarkers of exposure to potentially toxic constituents) and explore the identification and validation of biomarkers that may be useful in distinguishing EC from TC use. Study subjects will be dual users of TC and EC so that the investigators may compare both modalities of use in experienced users in a within-subject design.
The study will consist of two 1-week blocks (EC-only or TC-only conditions) with 4 days of outpatient ad libitum product use followed by 3 days in a clinical research ward to include a single-use pharmacokinetic study, monitoring of product use, subjective assessments, blood and urine collections to assess biomarkers, and a 24-hour period of cardiovascular monitoring. Two additional days at the end of the 2nd block will assess similar measurements during a period of nicotine-product abstention.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| EC Block1/TC Block 2 | Active comparator | Device: Tobacco Cigarette, Device: Electronic CigaretteParticipants will be randomized into one of two groups. In this group, participants will be assigned to Electronic Cigarettes only for Study Block #1, then crossover to Tobacco Cigarettes only for Study Block #2. |
| TC Block 1/EC Block 2 | Active comparator | Device: Tobacco Cigarette, Device: Electronic CigaretteParticipants will be randomized into one of two groups. In this group, participants will be assigned to Tobacco Cigarettes only for Study Block #1, then crossover to Electronic Cigarettes only for Study Block #2. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Healthy on the basis of medical history and limited physical examination as described below:
- Current regular "dual" user of both EC and conventional TC
- EC device is one of the most popular 1st, 2nd or 3rd generation brands (with the exception of rebuildable atomizers) as determined at time of study commencement
- Carbon monoxide ≥ 5 ppm or per discretion of Principal Investigator
- Saliva cotinine ≥50 ng/ml or urine cotinine
Key exclusion criteria (11 listed)
- Current regular use of selected psychiatric medications
- Current regular use of cardiovascular medications for cardiovascular conditions including hypertension (Example: beta and alpha-blockers)
- Current regular use of medications inducers of nicotine metabolizing enzymes CYP2A6 (Example: rifampicin, dexamethasone, phenobarbital, and other anticonvulsant drugs).
- Use of other tobacco products
- Pregnancy or breastfeeding (by history and pregnancy test)
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 |
|---|---|---|
| Tobacco CigaretteAlso: TC, CigaretteUsual brand tobacco cigarette smoked by study participant. | Device | EC Block1/TC Block 2, TC Block 1/EC Block 2 |
| Electronic CigaretteAlso: EC, E-cig, E-cigaretteUsual brand electronic cigarettes smoked by study participant. | Device | EC Block1/TC Block 2, TC Block 1/EC Block 2 |
Primary outcome
Standardized Session: Mean CMax
Time frame: Inpatient Day 1, Up to 4 Hours post Nicotine Administration
Maximum Plasma Nicotine Concentration (Cmax) (ng/mL)
Standardized Session: Mean TMax
Time frame: Inpatient Day 1, Up to 4 Hours post Session
Time (min) when Max Plasma Nicotine Concentration was achieved
Standardized Session: AUC 0-240
Time frame: Inpatient Day 1, Up to 4 Hours post Session
Plasma Nicotine area-under-the curve from 0 to 4 Hours (min*ng/ml)
PK-estimated Nicotine Dose
Time frame: Inpatient Day 1, Up to 4 Hours post Session
Estimated in dose received (in milligrams) during the Standardized Session.
6 secondary outcomes
Standardized Session: QSU Factor 1 (Vaping)
Time frame: Inpatient Day 1, Up to 4 Hours post Session
Standardized Session: Positive and Negative Affect Score (Negative Affect)
Time frame: Inpatient Day 1, Up to 4 Hours post Session
Standardized Session: Minnesota Nicotine Withdrawal Scale
Time frame: Inpatient Day 1, Up to 4 Hours post Session
Standardized Session: QSU Factor 2 (Vaping)
Time frame: Inpatient Day 1, Up to 4 Hours post Session
Standardized Session: QSU Factor 1 (Smoking)
Time frame: Inpatient Day 1, Up to 4 Hours post Session
Standardized Session: QSU Factor 2 (Smoking)
Time frame: Inpatient Day 1, Up to 4 Hours post Session
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33208019Benowitz NL, St Helen G, Nardone N, Addo N, Zhang JJ, Harvanko AM, Calfee CS, Jacob P 3rd. Twenty-Four-Hour Cardiovascular Effects of Electronic Cigarettes Compared With Cigarette Smoking in Dual Users. J Am Heart Assoc. 2020 Dec;9(23):e017317. doi: 10.1161/JAHA.120.017317. Epub 2020 Nov 19.
- Individual participant dataSharing planned: No
Related trials for Nicotine Dependence
Recruiting
Young Adult Tobacco/Nicotine and Cannabis Co-use
Tobacco Use Disorder, Nicotine Dependence
Recruiting
Social Media Support Groups for Adolescent Vaping Cessation
Vaping, Vaping Cessation
Recruiting
The INITIATE Study: Initiating Nicotine Dependence Treatment for Smokers Admitted to Emergency Departments
Nicotine Dependence, Cigarettes, Nicotine Withdrawal
Recruiting
Advanced Functional and Structural MRI Techniques for Neuropharmacological Imaging
Drug Abuse, Nicotine Dependence
RecruitingObservational study
§SMOKE Nicotine and Tobacco Youth Cohort
Tobacco Use Behavior, Nicotine Dependence Tobacco Product
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.
Neal L Benowitz, MD principal investigator
University of California, San Francisco
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Tobacco Cigarette and Electronic Cigarette in people with Nicotine Dependence, run by University of California, San Francisco at 2 sites 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 11 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 22 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
Yes. Results are posted in the registry (first posted 13 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Standardized Session: Mean CMax (time frame: Inpatient Day 1, Up to 4 Hours post Nicotine Administration). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02470754, which also lists 1 linked publication.
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 22 Jun 2023.