Efficacy and Neural Correlates of Personalized Treatment With Transdermal Nicotine Replacement

Study Overview
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Brief Summary
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This study involves the use of personalized nicotine patch dosing as a treatment strategy for smokers who cannot quit smoking after 2 weeks of using the standard nicotine patch dose. Functional Magnetic Resonance Imaging scans will also be obtained from all study participants before and after treatment. The first aim of the study is to determine if the treatment method under investigation is safe and more effective at increasing quit rates in smokers who do not respond to standard therapy.The second aim is to determine if there are any treatment- or cessation-related changes in brain function.

Detailed Description
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Nicotine Replacement Therapy (NRT) is limited in efficacy. One possible explanation for this limited efficacy is that the nicotine dose received in standard therapy is not enough to replace the amount of nicotine that smokers typically receive from their cigarettes. In an effort to counteract this problem, this study will increase the nicotine patch dose of smokers until they no longer feel the need to keep smoking or they cannot tolerate a higher nicotine dose. Smokers who cannot quit using 21 mg nicotine patch for 2 weeks will be randomized to either the experimental arm of the study where nicotine patch doses will be adjusted according to individual need or the positive control arm where standard NRT smoking cessation therapy will be employed. The primary outcome measure will be continuous abstinence during the last 4 weeks of treatment. In addition, participants will be assessed to see how treatment has impacted their resting state neural activity as well as their responsiveness to smoking and emotional cues. Follow up sessions will be used to assess long term abstinence as well as long term change in neural activation.

Official Title
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Efficacy and Neural Correlates of Personalized Treatment With Transdermal Nicotine Replacement: A Randomized, Controlled Pilot Study in Motivated Smokers Unable to Quit With Standard Dosing

Conditions
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Tobacco Use Disorder, Nicotine Dependence

Intervention / Treatment
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* Drug: Nicotine patch
* Drug: Nicotine mouthspray


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Daily tobacco smoker of Aged 19 to 65 years old Intending to quit smoking within the next 30 days Interested in using transdermal nicotine replacement therapy (nicotine patch) Exclusion Criteria: At least weekly use of tobacco products other than cigarettes Breast feeding, pregnancy or not using a reliable form of birth control Any generalized skin disorders precluding the use of the patch Immediate post-myocardial infarction period or life-threatening arrhythmias, severe or worsening angina pectoris or recent cerebral vascular accident Any clinically significant electrocardiogram (ECG) abnormalities Currently using NRT or other smoking cessation pharmacotherapy Any known hypersensitivity or allergies to any of the components comprising the nicotine patch MRI contraindications (e.g., metal in body, claustrophobia) as per the CAMH RIC screening questionnaire Diagnosis of terminal illness.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Arm<br>Escalating nicotine patch dose to satiety over 6 weeks with dosage depending on the number of cigarettes smoked per day and the occurrence of adverse effects | Drug: Nicotine patch<br> <br> * Other names: Nicoderm;|
| Active Comparator: Positive Control Arm<br>Nicotine patch dose of 21mg coupled with nicotine mouthspray which is to be used as needed. | Drug: Nicotine patch<br> <br> * Other names: Nicoderm;Drug: Nicotine mouthspray<br> <br> * Other names: Nicorette Quickmist;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 4 weeks continuous smoking abstinence | 4 weeks of abstinence without a single puff of a cigarette confirmed by self-report and exhaled carbon monoxide (CO less than or equal to 4ppm) | Treatment weeks 9-12 inclusive | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cue induced brain activation | Brain activation in response to viewing emotional and smoking cues as measured by fMRI | up to 6 month follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BOLD fMRI, Tobacco, Nicotine Patch, Nicotine Mouth Spray, Smoking Cessation, Quit Smoking, Abstinence, Dependence, Nicotine, Transdermal Nicotine Replacement Therapy, Functional Magnetic Resonance Imaging, Neuroimaging, Cue Reactivity, Resting State