Nicotine Dependence
Conditions
Brief 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, 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.
Interventions
DEVICETobacco Cigarette
Usual brand tobacco cigarette smoked by study participant.
DEVICEElectronic Cigarette
Usual brand electronic cigarettes smoked by study participant.
Sponsors
National Institutes of Health (NIH)
Roswell Park Cancer Institute
National Institute on Drug Abuse (NIDA)
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* 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 * 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
Exclusion criteria
* 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 * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PK-estimated Nicotine Dose | Inpatient Day 1, Up to 4 Hours post Session | Estimated in dose received (in milligrams) during the Standardized Session. |
| Standardized Session: Mean CMax | Inpatient Day 1, Up to 4 Hours post Nicotine Administration | Maximum Plasma Nicotine Concentration (Cmax) (ng/mL) |
| Standardized Session: Mean TMax | Inpatient Day 1, Up to 4 Hours post Session | Time (min) when Max Plasma Nicotine Concentration was achieved |
| Standardized Session: AUC 0-240 | Inpatient Day 1, Up to 4 Hours post Session | Plasma Nicotine area-under-the curve from 0 to 4 Hours (min\*ng/ml) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Standardized Session: QSU Factor 2 (Vaping) | Inpatient Day 1, Up to 4 Hours post Session | 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. |
| Standardized Session: QSU Factor 2 (Smoking) | Inpatient Day 1, Up to 4 Hours post Session | 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. |
| Standardized Session: QSU Factor 1 (Smoking) | Inpatient Day 1, Up to 4 Hours post Session | 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. |
| Standardized Session: QSU Factor 1 (Vaping) | Inpatient Day 1, Up to 4 Hours post Session | 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. |
| Standardized Session: Positive and Negative Affect Score (Negative Affect) | Inpatient Day 1, Up to 4 Hours post Session | 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. |
| Standardized Session: Minnesota Nicotine Withdrawal Scale | Inpatient Day 1, Up to 4 Hours post Session | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Standardized Session: Half-life | Inpatient Day 1, Up to 4 Hours post Session | Estimated Time (min) to reduce the plasma nicotine concentration by half based on observed pharmacokinetics. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Completers all completed | 36 |
| Total | 36 |
Baseline characteristics
| Characteristic | Completers |
|---|---|
| Age, Continuous | 35.4 years STANDARD_DEVIATION 11.7 |
| Cigarettes per day | 12.9 Cigarettes per day STANDARD_DEVIATION 6.4 |
| Days of EC use in past 30 | 22.6 Days STANDARD_DEVIATION 7.3 |
| E-Cigarette Use index | 6.5 units on a scale STANDARD_DEVIATION 6.5 |
| EC times per day | 8.1 Sessions per day STANDARD_DEVIATION 7.2 |
| EC to TC use ratio | 0.57 ratio STANDARD_DEVIATION 0.56 |
| EC type Cig-a-like | 12 Participants |
| EC type Fixed-power | 15 Participants |
| EC type Pod | 3 Participants |
| EC type Variable-power | 6 Participants |
| Fagerstrom Test for Cigarette Dependence | 4.4 units on a scale STANDARD_DEVIATION 2 |
| Flavor category Dessert/candy | 8 Participants |
| Flavor category Fruit | 5 Participants |
| Flavor category Menthol | 5 Participants |
| Flavor category Tobacco | 18 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants |
| Race/Ethnicity, Customized Black | 3 Participants |
| Race/Ethnicity, Customized Latino | 4 Participants |
| Race/Ethnicity, Customized Mixed | 5 Participants |
| Race/Ethnicity, Customized White | 22 Participants |
| Region of Enrollment United States | 36 participants |
| Salivary cotinine | 189 ng/mL STANDARD_DEVIATION 92.8 |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 28 Participants |
| Time to first cigarette 30-60 min | 8 Participants |
| Time to first cigarette 5-30 min | 21 Participants |
| Time to first cigarette ≤ 5 min | 6 Participants |
| Time to first cigarette >60 min | 1 Participants |
| Time to first vape 30-60 min | 4 Participants |
| Time to first vape 5-30 min | 12 Participants |
| Time to first vape ≤ 5 min | 1 Participants |
| Time to first vape > 60 min | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 38 | 0 / 38 |
| other Total, other adverse events | 0 / 38 | 0 / 38 |
| serious Total, serious adverse events | 0 / 38 | 0 / 38 |
Outcome results
Primary
PK-estimated Nicotine Dose
Estimated in dose received (in milligrams) during the Standardized Session.
Time frame: Inpatient Day 1, Up to 4 Hours post Session
Population: Pod Users Excluded
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Electronic Cigarette | PK-estimated Nicotine Dose | 0.9 mg | Standard Deviation 0.7 |
| Combustible Cigarette | PK-estimated Nicotine Dose | 2.2 mg | Standard Deviation 1.2 |
Primary
Standardized Session: AUC 0-240
Plasma Nicotine area-under-the curve from 0 to 4 Hours (min\*ng/ml)
Time frame: Inpatient Day 1, Up to 4 Hours post Session
Population: Pod users excluded
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Electronic Cigarette | Standardized Session: AUC 0-240 | 550 min*ng/ml | Standard Deviation 438 |
| Combustible Cigarette | Standardized Session: AUC 0-240 | 1368 min*ng/ml | Standard Deviation 665 |
Primary
Standardized Session: Mean CMax
Maximum Plasma Nicotine Concentration (Cmax) (ng/mL)
Time frame: Inpatient Day 1, Up to 4 Hours post Nicotine Administration
Population: Pod users excluded
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Electronic Cigarette | Standardized Session: Mean CMax | 6.1 ng/mL | Standard Deviation 5.5 |
| Combustible Cigarette | Standardized Session: Mean CMax | 20.2 ng/mL | Standard Deviation 11.1 |
Primary
Standardized Session: Mean TMax
Time (min) when Max Plasma Nicotine Concentration was achieved
Time frame: Inpatient Day 1, Up to 4 Hours post Session
Population: Pod users excluded
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Electronic Cigarette | Standardized Session: Mean TMax | 6.5 minutes | Standard Deviation 5.4 |
| Combustible Cigarette | Standardized Session: Mean TMax | 2.7 minutes | Standard Deviation 2.4 |
Secondary
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.
Time frame: Inpatient Day 1, Up to 4 Hours post Session
Population: Pod Users Excluded
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Electronic Cigarette | Standardized Session: Minnesota Nicotine Withdrawal Scale | 10.8 score on a scale | Standard Deviation 7.9 |
| Combustible Cigarette | Standardized Session: Minnesota Nicotine Withdrawal Scale | 9.6 score on a scale | Standard Deviation 7.4 |
Secondary
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.
Time frame: Inpatient Day 1, Up to 4 Hours post Session
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Electronic Cigarette | Standardized Session: Positive and Negative Affect Score (Negative Affect) | 14.3 score on a scale | Standard Deviation 5.6 |
| Combustible Cigarette | Standardized Session: Positive and Negative Affect Score (Negative Affect) | 14.0 score on a scale | Standard Deviation 5 |
Secondary
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.
Time frame: Inpatient Day 1, Up to 4 Hours post Session
Population: Pod Users Excluded
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Electronic Cigarette | Standardized Session: QSU Factor 1 (Smoking) | 22.9 score on a scale | Standard Deviation 9.8 |
| Combustible Cigarette | Standardized Session: QSU Factor 1 (Smoking) | 24.2 score on a scale | Standard Deviation 9.9 |
Secondary
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.
Time frame: Inpatient Day 1, Up to 4 Hours post Session
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Electronic Cigarette | Standardized Session: QSU Factor 1 (Vaping) | 23.9 score on a scale | Standard Deviation 8.6 |
| Combustible Cigarette | Standardized Session: QSU Factor 1 (Vaping) | 20.7 score on a scale | Standard Deviation 10 |
Secondary
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.
Time frame: Inpatient Day 1, Up to 4 Hours post Session
Population: Pod Users Excluded
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Electronic Cigarette | Standardized Session: QSU Factor 2 (Smoking) | 14.4 score on a scale | Standard Deviation 6.6 |
| Combustible Cigarette | Standardized Session: QSU Factor 2 (Smoking) | 14.1 score on a scale | Standard Deviation 7.2 |
Secondary
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.
Time frame: Inpatient Day 1, Up to 4 Hours post Session
Population: Pod Users Excluded
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Electronic Cigarette | Standardized Session: QSU Factor 2 (Vaping) | 14.9 score on a scale | Standard Deviation 6.8 |
| Combustible Cigarette | Standardized Session: QSU Factor 2 (Vaping) | 13.0 score on a scale | Standard Deviation 7 |
Other Pre-specified
Standardized Session: Half-life
Estimated Time (min) to reduce the plasma nicotine concentration by half based on observed pharmacokinetics.
Time frame: Inpatient Day 1, Up to 4 Hours post Session
Population: Pod Users Excluded
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Electronic Cigarette | Standardized Session: Half-life | 137.6 min | Standard Deviation 39.3 |
| Combustible Cigarette | Standardized Session: Half-life | 121.2 min | Standard Deviation 33.9 |