Effects of Random Nicotine Delivery on Smoking Cessation

Study Overview
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Brief Summary
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The objective of this study is to determine whether treatment with random nicotine delivery via a nicotine film both before and after the target quit date will facilitate smoking cessation relative to treatment with steady state delivery or placebo. The investigators hypothesize that smoking cessation will be greater in subjects assigned to a random nicotine delivery regimen (as compared to those assigned to a steady state or placebo regimen). The nicotine film product is not part of the standard of care and is not available in non-investigational settings in the United States.

Detailed Description
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This project is a prospective parallel-group, randomized, double-blind, placebo-controlled study in which 45 current cigarette smokers who are interested in quitting will be randomly allocated to one of three possible nicotine film treatment regimens: Random nicotine delivery (a combination of four 0 mg and 4 mg films daily not to exceed three non-consecutive 4 mg films in one day and to maintain an average of 8 mg of nicotine per day through 7 days for 6 weeks total). Steady state nicotine delivery (2, 2, 2, 2 mg films daily for 6 weeks total) Placebo delivery (0, 0, 0, 0 mg films daily for 6 weeks total) Prior to assignment in one of the above treatment groups, all participants will take part in a 1-week baseline period to assess normal smoking behavior and nicotine dependence. Following randomization to their assigned treatment group at Visit 2, participants will be instructed to smoke cigarettes as they feel necessary over the next two weeks while using the nicotine films as directed (i.e., one film every 3-4 hours for a total of four films per day). After two weeks of pre-cessation treatment, participants will be asked completely cease cigarette smoking and to only use their assigned nicotine films as directed. Participants will be supported in their quitting efforts with regular contacts both in person at the Penn State Milton S. Hershey Medical Center and over the phone.

Official Title
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Effects of Random Nicotine Delivery on Smoking Cessation

Conditions
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Smoking Cessation, Cigarette Smoking, Smoking (Tobacco) Addiction

Intervention / Treatment
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* Drug: Nicotine Film


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18-55 Smoke ≥10 cigarettes/day for at least the past 12 months Exhaled CO measurement ≥6 ppm at baseline visit Interested in completely ceasing cigarette consumption and using a nicotine film product as directed Willing to attend regular visits over a 6-week period (not planning to move, not planning extended vacation, no planned surgeries) Able to read and write in English Able to understand and consent to study procedures Exclusion Criteria: Unstable or significant medical conditions and conditions such as elevated blood pressure (systolic >159 mmHg or diastolic >99mmHg at baseline), COPD, and those conditions that are likely to affect biomarker data such as kidney or liver disease Individuals with sodium-restricted diet, heart disease, recent heart attack, irregular heartbeat, stomach ulcers, or diabetes as well as those taking prescription medications for depression or asthma as indicated under Warnings section on FDA approved NRT Drug Facts Label More than weekly use in the past 3 months of illegal drugs or prescription drugs that are not being used for medically prescribed purposes Use of non-cigarette nicotine delivery product in the prior 7 days (including cigars, pipes, chew, snus, hookah, electronic cigarette and marijuana mixed with tobacco) Use of an FDA approved cessation medication in the past 7 days (any NRT, Chantix, Wellbutrin) Women who are pregnant (verified by urine pregnancy test at baseline visit), trying to become pregnant, or nursing Uncontrolled mental illness or substance abuse or inpatient treatment for these conditions in the past 6 months Any previous adverse reaction to NRT Any other condition, serious illness, or situation that would, in the investigator's opinion, make it unlikely that the participant could comply with the study protocol Other member of household currently participating in the study

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Random Nicotine Delivery<br>One 0 mg or 4 mg nicotine film every 3-4 hours for a total of four films per day (not to exceed three non-consecutive 4 mg films in one day) for 6 weeks. | Drug: Nicotine Film<br>* Three doses of nicotine films will be used in this project: 0 mg, 2 mg, and 4 mg. The active pharmaceutical ingredient in the nicotine film product is nicotine polacrilex (20%, USP). The film has a muco-adhesive property and allows nicotine to be absorbed through the oral mucosa. After placement in the oral cavity, the nicotine film dissolves in less than five minutes. The film is in the form of 1 inch x 1 inch square and weighs about 100 mg. Nicotine films are not available in the United States in a non-investigational setting.<br>|
| Active Comparator: Steady State Nicotine Delivery<br>One 2 mg nicotine film every 3-4 hours for a total of four films per day for 6 weeks. | Drug: Nicotine Film<br>* Three doses of nicotine films will be used in this project: 0 mg, 2 mg, and 4 mg. The active pharmaceutical ingredient in the nicotine film product is nicotine polacrilex (20%, USP). The film has a muco-adhesive property and allows nicotine to be absorbed through the oral mucosa. After placement in the oral cavity, the nicotine film dissolves in less than five minutes. The film is in the form of 1 inch x 1 inch square and weighs about 100 mg. Nicotine films are not available in the United States in a non-investigational setting.<br>|
| Placebo Comparator: Placebo Control<br>One 0 mg nicotine film every 3-4 hours for a total of four films per day for 6 weeks. | Drug: Nicotine Film<br>* Three doses of nicotine films will be used in this project: 0 mg, 2 mg, and 4 mg. The active pharmaceutical ingredient in the nicotine film product is nicotine polacrilex (20%, USP). The film has a muco-adhesive property and allows nicotine to be absorbed through the oral mucosa. After placement in the oral cavity, the nicotine film dissolves in less than five minutes. The film is in the form of 1 inch x 1 inch square and weighs about 100 mg. Nicotine films are not available in the United States in a non-investigational setting.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Number of Cigarettes Smoked Per Day (CPD) | CPD is measured with the use of daily cigarette logs which are completed daily by participants and returned to the study center at each visit. The CPD measure will be the average of the past 7 days. | Baseline and 4 weeks after Target Quit Date | 
| Change in Exhaled Carbon Monoxide (CO) Measurement | Mean change in exhaled CO (parts per million [ppm]) | Baseline and 4 weeks after Target Quit Date | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Questionnaire of Smoking Urges-Brief (QSU-Brief) Total Score | The QSU-Brief, with a possible total score range of 10 to 70, is an instrument used to measure cigarette craving. A score of 10 on this scale indicates very low cigarette craving, while a score of 70 indicates very high cigarette craving. | Baseline and 4 weeks after Target Quit Date | 
| Change in Fagerstrom Test for Nicotine Dependence (FTND) Total Score | Nicotine dependence will be assessed via the FTND, a measure with total scores ranging from 0 (very low dependence) to 10 (very high dependence). | Baseline and 4 weeks after Target Quit Date | 
| Subjective Ratings Scale for Nicotine Film Use | The scale is comprised of 21 items. Each item is rated on a scale 1-7, where 1 is equal to not at all and 7 is equal to extremely. The total score is the average score of all 21 items. The total score ranges from 1-7. | 4 weeks after Target Quit Date | 
| Side Effects From Nicotine Film Use | Total score ranges from 0 - 36 with lower scores indicating lesser side effects. | 4 weeks after Target Quit Date | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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smoking cessation, nicotine film, nicotine delivery, random nicotine delivery