Effect of the Electronic Cigarette on Withdrawal Symptoms

Study Overview
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Brief Summary
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Study rationale: Sensory/behavioural elements of smoking play a role in smoking behaviour and may have a potential to assist smoking cessation. Among current treatments for smokers, only the nicotine inhalator is attempting to address such factors. The inhalator's efficacy does not exceed that of the other nicotine replacement therapy (NRT) products, but it mimics the relevant sensory input to only a limited extent, and its nicotine delivery is dependent on intensive puffing. Recently a new product, the Electronic Cigarette (E-C) has become available, which provides a more realistic behaviour and sensory replacement for smoking and can provide good nicotine levels with less effort. Primary objective: To compare E-C and nicotine inhalator in their effects on tobacco withdrawal symptoms over 24hr abstinence. Hypotheses: E-C will be more effective than the inhalator in reducing withdrawal symptoms and craving and elicit more favorable user ratings. It will also provide higher nicotine levels. Study design: In a cross-over study, participants will be randomized to the sequence of conditions and provide baseline measures and samples for salivary cotinine analysis. They will be asked to abstain from smoking their usual cigarettes and use the allocated product over 24 hours. They will return to the study centre the following day, and complete measures of craving and withdrawal, ratings of subjective and sensory effects of the products, product satisfaction, and adverse effects. They will also provide saliva samples for cotinine analysis. Abstinence from smoking will be verified with CO readings.

Detailed Description
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There is considerable interest in E-Cs at the moment and the study would provide information on whether the E-C surpasses the tried and tested nicotine inhalator. If so, it would open a possibility of its utilization in smoking cessation, and provide encouragement for further examination of the role of sensorimotor replacements in the treatment of tobacco dependence.

Official Title
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Phase 4 Study to Compare of the Effects of the Electronic Cigarette and Nicotine Inhalator on Tobacco Withdrawal Symptoms Over 24 Hours of Abstinence

Conditions
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Mental and Behavioral Disorders, Withdrawal State

Intervention / Treatment
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* Drug: Nicotine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Volunteers smoking at least 12 cigarettes per day First cigarette smoked within 60 minutes of waking up Willing to abstain from smoking for one day in 2 consecutive weeks. Exclusion Criteria: Under 18 years of age Current psychiatric illness Pregnant or breastfeeding Enrollment in other research projects Used electronic cigarette and/or nicotine inhalator before

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Electronic cigarette<br>We analysed 15 brands of the most popular E-Cs in the UK, EU and US for nicotine levels in the mist. Vapours were generated from cartridges of various nicotine content using a standard single-port linear smoking machine with a puff volume of 70 ml, 1 puff every 7 sec., and a puff duration of 1.8 sec (based on averaged puffing conditions from 10 E-C users found during preliminary studies). Nicotine was absorbed in two sequential washing bottles with methanol and internal standards and analysed with gas chromatography. One brand was selected for this study as it consistently delivers about 1mg of nicotine with 20 puffs. | Drug: Nicotine<br>* Inhalation of nicotine.<br>* Other names: Nicorette inhalator;|
| Active Comparator: Nicotine Inhalator<br>The inhalator consists of a nicotine cartridge which is placed into a plastic mouthpiece. One cartridge contains 10mg of nicotine of which 4mg of nicotine can be extracted. Nicotine is delivered mainly through the oral cavity, throat, and upper respiratory tract with a minor fraction reaching the lungs. A single cartridge can be used for one 20-minute period of continuous puffing or periodic use of up to 400 puffs per cartridge. | Drug: Nicotine<br>* Inhalation of nicotine.<br>* Other names: Nicorette inhalator;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of E-C and Inhalator in Effects on Withdrawal Over 24 Hours of Use. | Mood and Physical Symptoms Scale (MPSS): Measure of severity of urges to smoke and tobacco withdrawal symptoms. A five-point scale is used to rate 'How much of the time have you felt the urge to smoke in the past week?' ((1) 'not at all' to (5) 'almost all of the time') and 'How strong have the urges been?' ('no urges' to 'very strong'). Clients also rate depression, irritability, restlessness, hunger, poor concentration, poor sleep at night, and anxiety during the past week ((1)=not at all to (5)=extremely). The combined score to questions on depression, irritability, restlessness, hunger, and poor concentration are averaged to give the MPSS score. A higher score means a more severe rating of withdrawal. The primary outcome is a change in MPSS score between baseline and 24 hours (value at 24 hours minus value at baseline). Therefore, a smaller change in MPSS score represents a smaller increase in tobacco withdrawal symptoms. | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Salivary Cotinine Levels After 24-hour Use. | Cotinine is a measure sensitive enough to detect effects of a switch to different nicotine products and salivary cotinine was shown to be dependent on nicotine mouth exposure. The results show the mean change in salivary cotinine in each study arm (all study participants). | 24 hours | 
| Reinforcing Effects of Smoking | Modified Cigarette Evaluation Questionnaire (mCEQ): Measure of reinforcing effects of smoking (pleasant feeling). Mean pleasant feeling from using product (rating 0-4). Higher value indicating the higher rating of pleasure. | 24 hours | 
| Airway Sensations | Sensory effects: Measure of airway sensations (throat and chest). Mean enjoyment score (rating 0-4), higher the score indicating increased enjoyment. | 24 hours | 
| Product Satisfaction | Product satisfaction: Ratings of product satisfaction (when compared to cigarettes). Rating 0-4, with higher value indicating higher satisfaction ratings. | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nicotine, inhalator, electronic cigarette, tobacco