Nicotine Delivery From Novel Non-Tobacco Electronic System in Smokers

Study Overview
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Brief Summary
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This randomized pilot clinical trial studies nicotine delivery from novel non-tobacco electronic system (ENDS) in smokers. Studying the levels of nicotine delivered by various types and brands of ENDS to the bloodstream, and comparing this to the levels delivered from conventional cigarettes (the participant's own brand) may help provide information about the use of nicotine-containing products that may help inform/reform current tobacco policy, practice, and harm reduction approaches.

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the levels of nicotine effectively delivered by various types and brands of ENDS to the bloodstream and compare them to levels delivered from conventional cigarettes. (Study 1) II. Explore the effect of flavorings added to nicotine solution on puffing topography and nicotine delivery and, assess and compare short-term functional nicotine effects of the different products by using subjective measures such as relief of craving and withdrawal symptoms. (Study 2) SECONDARY OBJECTIVES: I. Determine the amounts of nicotine present in various brands and types of ENDS. (Study 3) II. Determine nicotine yields in vapors from various types of ENDS under laboratory conditions. (Study 4) TERTIARY OBJECTIVES: I. Develop a standardized testing protocol for ENDS that will reflect users' puffing behavior and product characteristics. II. Develop and validate the analytical method for analysis of nicotine content in the vapor. III. Propose a standardized puffing regimen for generating vapors for analytical purposes: Such a testing protocol will reflect the puffing behavior observed among ENDS users and should be specific to ENDS type. OUTLINE: Participants are randomized to 1 of 2 arms. ARM I (Study 1): Participants are asked to smoke ad lib a single cigarette of their own brand and provided with a different type of ENDS product at each visit (e-cigarette, disposable e-cigarette, eGo, personal vaporizer, e-cigar, and e-pipe) over 3.5-4 hours at least 7 days apart for 7 weeks. Participants are provided with cartridges of the same amounts of nicotine with regular (tobacco) or menthol flavor according to smoker's preference, instructed on how to use the product, asked to practice using it for 7 days, and return to the study center for their next visit. ARM II (Study 2): Participants are asked to smoke ad lib a single cigarette of their own brand and provided with the BLU e-cigarette ENDS product with nicotine solution of one of five flavors over 3.5-4 hours at least 7 days apart for 6 weeks. Participants are provided with cartridges of maximum available amounts of nicotine and different flavors at each visit, instructed on how to use the product, asked to practice using it for 7 days, and return to the study center for their next visit.

Official Title
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Nicotine Delivery From Novel Non-tobacco Electronic Systems (ENDS)

Conditions
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Cigarette Smoker, Current Smoker, Healthy Subject

Intervention / Treatment
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* Other: Electronic Cigarette
* Other: Electronic Cigarette
* Other: Laboratory Biomarker Analysis
* Other: Pharmacological Study
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy on the basis of medical history Current moderate-to-heavy smoker as determined by: Has smoked >=10 cigarettes per day regularly for the past year (by history) and (>=5 cigarettes per day Study 2 ONLY) Has an expired carbon monoxide (CO) at screening visit of 8 parts per million (ppm) or more (6 ppm or more Study 2 ONLY) Nicotine dependence assessed as > 4 with the Fagerstrom Test for Nicotine Dependence Willingness to abstain from smoking for 8 hours (overnight abstinence) prior to study visits Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure Exclusion Criteria: Unstable medical conditions (such as unstable heart disease, uncontrolled hypertension, thyroid disease, diabetes, renal or liver impairment, glaucoma, or prostatic hypertrophy) or psychiatric condition (such as current major depression, history of schizophrenia or bipolar disorder, or current regular use of psychiatric medications such as major tranquilizers and antidepressants Pregnancy or lactation (by history) or positive pregnancy test at screening visit Positive urine drug test at screening visit History of serious side effects from nicotine or from any nicotine replacement therapies Alcohol or illicit drug dependence within the past 12 months (by history and urine tests) Concurrent participation in another clinical trial Unable to communicate in English Unwilling or unable to follow protocol requirements Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to receive study intervention

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (different type of ENDS product at each visit)<br>Participants are asked to smoke ad lib a single cigarette of their own brand and provided with a different type of ENDS product at each visit (e-cigarette, disposable e-cigarette, eGo, personal vaporizer, e-cigar, and e-pipe) over 3.5-4 hours at least 7 days apart for 7 weeks. Participants are provided with cartridges of the same amounts of nicotine with regular (tobacco) or menthol flavor according to smoker's preference, instructed on how to use the product, asked to practice using it for 7 days, and return to the study center for their next visit. | Other: Electronic Cigarette<br>* Receive different type of ENDS product at each visit<br>* Other names: Electronic Nicotine Delivery System;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Other: Pharmacological Study<br>* Correlative studies<br>Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Experimental: Arm II (BLU e-cigarette ENDS product with different flavors)<br>Participants are asked to smoke ad lib a single cigarette of their own brand and provided with the BLU e-cigarette ENDS product with nicotine solution of one of five flavors over 3.5-4 hours at least 7 days apart for 6 weeks. Participants are provided with cartridges of maximum available amounts of nicotine and different flavors at each visit, instructed on how to use the product, asked to practice using it for 7 days, and return to the study center for their next visit. | Other: Electronic Cigarette<br>* Receive BLU e-cigarette ENDS product<br>* Other names: Electronic Nicotine Delivery System;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Other: Pharmacological Study<br>* Correlative studies<br>Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine Levels of nicotine effectively delivered by various types and brands of ENDS to the bloodstream and compare them to levels delivered from conventional cigarettes | The maximum concentration of nicotine in plasma (Cmax) will be determined for each product. | Up to 1 year | 
| Levels of nicotine effectively delivered by various types and brands of ENDS to the bloodstream and compare them to levels delivered from conventional cigarettes | Time to maximum concentration (Tmax) will be determined for each product . | Up to 1 year | 
| Levels of nicotine effectively delivered by various types and brands of ENDS to the bloodstream and compare them to levels delivered from conventional cigarettes | Area under the plasma concentration versus time curve (AUC) will be determined for each product. | up to 1 year | 
| Changes in withdrawal symptoms | Will be measured with Minnesota Withdrawal Scale | up to 1 year | 
| Subjective nicotine effect will be analyzed | Will be measured with Drug Effect Questionnaire | up to 1 year | 
| Changes in feelings and emotions | Will be measured with The Positive Negative Affect Scale | up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amounts of nicotine present in various brands and types of ENDS (Study 3) | Nicotine content (mean, median, minimum and maximum) will be determined for each product | Up to 1 year | 
| Nicotine yields in vapors from various types of ENDS under laboratory conditions (Study 4) | Nicotine yield in vapor will be determined for each product. | Up to 1 year |