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| ID | Type | Description | Link |
|---|---|---|---|
| R01DA039264 | U.S. NIH Grant/Contract | View source | |
| NCI-2018-02897 | Registry Identifier | NCI Clinical Trials Reporting Program |
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| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
| Roswell Park Cancer Institute | OTHER |
| National Institute on Drug Abuse (NIDA) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tobacco Cigarette | Device | Usual brand tobacco cigarette smoked by study participant. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Standardized Session: Mean CMax | Maximum Plasma Nicotine Concentration (Cmax) (ng/mL) | Inpatient Day 1, Up to 4 Hours post Nicotine Administration |
| Standardized Session: Mean TMax | Time (min) when Max Plasma Nicotine Concentration was achieved | 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) | Inpatient Day 1, Up to 4 Hours post Session |
| PK-estimated Nicotine Dose | Estimated in dose received (in milligrams) during the Standardized Session. | Inpatient Day 1, Up to 4 Hours post Session |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Standardized Session: Half-life | Estimated Time (min) to reduce the plasma nicotine concentration by half based on observed pharmacokinetics. | Inpatient Day 1, Up to 4 Hours post Session |
Inclusion Criteria:
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
Age: ≥ 21 years
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Neal L Benowitz, MD | University of California, San Francisco | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| San Francisco General Hospital (SFGH) | San Francisco | California | 94110 | United States | ||
| University of California, San Francisco (UCSF) |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33208019 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | EC Block1/TC Block 2 | 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. Tobacco Cigarette: Usual brand tobacco cigarette smoked by study participant. Electronic Cigarette: Usual brand electronic cigarettes smoked by study participant. |
| FG001 | TC Block 1/EC Block 2 | 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. Tobacco Cigarette: Usual brand tobacco cigarette smoked by study participant. Electronic Cigarette: Usual brand electronic cigarettes smoked by study participant. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Completers | all completed |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Standardized Session: Mean CMax | Maximum Plasma Nicotine Concentration (Cmax) (ng/mL) | Pod users excluded | Posted | Mean | Standard Deviation | ng/mL | Inpatient Day 1, Up to 4 Hours post Nicotine Administration |
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Study participation lasted 2 weeks.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Electronic Cigarette | Electronic cigarette ARM | 0 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Natalie Nardone, PhD | University of California, San Francisco | 415-514-1450 | natalie.nardone@ucsf.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 26, 2018 | Sep 25, 2019 | Prot_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 15, 2019 | Apr 22, 2019 | SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Oct 9, 2017 | Apr 15, 2019 | ICF_000.pdf |
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| ID | Term |
|---|---|
| D014029 | Tobacco Use Disorder |
| ID | Term |
|---|---|
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| Electronic Cigarette | Device | Usual brand electronic cigarettes smoked by study participant. |
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| 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. | 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. | 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. | 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. | 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. | Inpatient Day 1, Up to 4 Hours post Session |
| San Francisco |
| California |
| 94110 |
| United States |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Cigarettes per day | Mean | Standard Deviation | Cigarettes per day |
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| Days of EC use in past 30 | Mean | Standard Deviation | Days |
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| EC times per day | Mean | Standard Deviation | Sessions per day |
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| E-Cigarette Use index | E-Cigarette (EC) Use Index calculated as a function of (# of E-Cigarette Sessions Per Day) x E-Cigarette use days per Month) /30. Ranges from [0 to Infinity]. With lower values indicating minimal e-cigarette use and higher values indicating heavy E-Cigarette Use. | Mean | Standard Deviation | units on a scale |
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| EC to TC use ratio | Mean | Standard Deviation | ratio |
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| Fagerstrom Test for Cigarette Dependence | The Fagerström Test for Nicotine Dependence is a standard instrument for assessing the intensity of physical addiction to nicotine.It contains six items that evaluate the quantity of cigarette consumption, the compulsion to use, and dependence.Questionnaire scored 0-10 points with Total Score equal to the sum of all points.A patient who scores between 1 and 2 Test is classified as having a low dependence on nicotine. A patient who scores 5 and over would be considered highly dependent on nicotine. | Mean | Standard Deviation | units on a scale |
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| Time to first cigarette | Participant response to "How soon after you wake up do you usually have your first cigarette?" at baseline visit | Count of Participants | Participants |
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| Time to first vape | Participant response to "How soon after you wake up do you usually first use your e-cigarette?" at baseline visit | Count of Participants | Participants |
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| Salivary cotinine | Mean | Standard Deviation | ng/mL |
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| EC type | Count of Participants | Participants |
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| Flavor category | Count of Participants | Participants |
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| Participants |
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| Primary | Standardized Session: Mean TMax | Time (min) when Max Plasma Nicotine Concentration was achieved | Pod users excluded | Posted | Mean | Standard Deviation | minutes | Inpatient Day 1, Up to 4 Hours post Session |
|
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| Primary | Standardized Session: AUC 0-240 | Plasma Nicotine area-under-the curve from 0 to 4 Hours (min*ng/ml) | Pod users excluded | Posted | Mean | Standard Deviation | min*ng/ml | Inpatient Day 1, Up to 4 Hours post Session |
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|
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| Primary | PK-estimated Nicotine Dose | Estimated in dose received (in milligrams) during the Standardized Session. | Pod Users Excluded | Posted | Mean | Standard Deviation | mg | Inpatient Day 1, Up to 4 Hours post Session |
|
|
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| 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. | Posted | Mean | Standard Deviation | score on a scale | Inpatient Day 1, Up to 4 Hours post Session |
|
|
|
| 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. | Posted | Mean | Standard Deviation | score on a scale | Inpatient Day 1, Up to 4 Hours post Session |
|
|
|
| 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. | Pod Users Excluded | Posted | Mean | Standard Deviation | score on a scale | Inpatient Day 1, Up to 4 Hours post Session |
|
|
|
| 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. | Pod Users Excluded | Posted | Mean | Standard Deviation | score on a scale | Inpatient Day 1, Up to 4 Hours post Session |
|
|
|
| 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. | Pod Users Excluded | Posted | Mean | Standard Deviation | score on a scale | Inpatient Day 1, Up to 4 Hours post Session |
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|
| 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. | Pod Users Excluded | Posted | Mean | Standard Deviation | score on a scale | Inpatient Day 1, Up to 4 Hours post Session |
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| Other Pre-specified | Standardized Session: Half-life | Estimated Time (min) to reduce the plasma nicotine concentration by half based on observed pharmacokinetics. | Pod Users Excluded | Posted | Mean | Standard Deviation | min | Inpatient Day 1, Up to 4 Hours post Session |
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| 38 |
| 0 |
| 38 |
| 0 |
| 38 |
| EG001 | Combustible Cigarette | Tobacco Cigarette ARM | 0 | 38 | 0 | 38 | 0 | 38 |
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