The Role of Nicotine Dose and Route of Delivery in Affecting Adoption of E-cigarettes and Reducing Exposure to Toxic Combustion Products

Study Overview
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Brief Summary
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This study plans to investigate whether using electronic cigarettes (e-cigarettes) or skin patches containing nicotine affects switching from smoking conventional combustible (burning) cigarettes.

Detailed Description
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This study proposes to assess the relative role of nicotine dose and route of delivery in affecting successful switching from combustible cigarettes to e-cigarettes, as well as concomitant reductions in ad libitum cigarette smoking and exposure to harmful and potentially harmful constituents of combustion. The strategy will be to assess adoption of e-cigarette use and concomitant reduction in ad libitum smoking of subjects' usual brands of cigarettes over an 8-week period, during which they will receive nicotine or non-nicotine e-cigarettes, and nicotine skin patches. The nicotine patches will not be used as a therapeutic treatment in this study, but rather as a way to manipulate the nicotine dose, while varying the rate and route of nicotine delivery. Behavioral or habit aspects of e-cigarette use will be controlled for by the groups receiving non-nicotine e-cigarettes. Initially the study design included placebo patch control conditions, but due to limitations in budget and period of support, enrollment in these these arms was discontinued. All participants currently receive active nicotine patches.

Official Title
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The Role of Nicotine Dose and Route of Delivery in Affecting Adoption of E-cigarettes and Reducing Exposure to Toxic Combustion Products

Conditions
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Nicotine Dependence, Cigarettes

Intervention / Treatment
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* Drug: Nicotine patch
* Other: Placebo patch
* Other: E-cigarettes
* Other: Non-nicotine e-cigarettes


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Smoke an average of at least 10 cigarettes per day; Have smoked at least one cumulative year; Have an expired air CO reading of at least 10ppm; Have a body weight of > 110 lbs. (50 kg) and ≤ 300 lbs. (136 kg); Are able to read and understand English; Potential subjects of child bearing potential must agree to use acceptable contraception during their participation in this study. Potential subjects must agree to avoid the following during their participation in this study: Participation in any other nicotine-related modification strategy outside of this protocol; Use of tobacco products other than cigarettes, including pipe tobacco, cigars, snuff, and chewing tobacco; Use of e-cigarettes other than the ones provided during the study; Use of experimental (investigational) drugs or devices; Use of illegal drugs; Use of exclusionary medications. Exclusion Criteria: Seeking treatment for nicotine dependence. Hypertension - systolic BP > 160 mm Hg, diastolic BP > 100 mm Hg. Individuals with a history of hypertension may be allowed to participate in the study if the study physician or medical provider determines that the condition is stable and will not jeopardize the individual's safety. Hypotension (with symptoms) - systolic BP < 90 mm Hg, diastolic BP < 60 mm Hg. Coronary heart disease with symptoms (e.g., chest pain) Heart attack in the past year Cardiac rhythm disorder (irregular heart rhythm with symptoms) Chest pain in the last month (unless history indicates a non-cardiac source) Symptomatic heart disorder such as heart failure Advanced liver or kidney disease that requires medication or dialysis, paracentesis Major gastrointestinal illness (e.g. Celiac disease, Crohn's dx Ulcerative Colitis) Bleeding stomach ulcers in the past 30 days Lung disease that requires oxygen Major brain disorder (including stroke with residual deficit, brain tumor, and seizure disorder) Migraine headaches that occur more frequently than once per week Recent, unexplained fainting spells Problems giving blood samples Diabetes with insulin use or with HbA1C over 7% Current cancer or treatment for cancer in the past six months (except basal or squa-mous cell skin cancer) HIV, Hepatitis B, or Hepatitis C History of Tuberculosis or recent positive purified protein derivative (PPD) Other major medical condition (as determined by study physician) Currently symptomatic psychiatric disease (as determined by study physician) Psychosis, bipolar disorder, or psychiatric hospitalization within the past 12 months Suicidal ideation (thinking about ways to commit suicide) (within the past 12 months) or a lifetime occurrence of attempted suicide; Current depression - The Patient Health Questionnaire PHQ-9 for Depression will be used to screen for current (within 2 weeks) depression. Potential subjects who score >9 (or who score >0 on item #9 (Thoughts that you would be better off dead, or of hurting yourself in some way) will be excluded from study participation, and, at the discretion of the study physician, referred to appropriate psychiatric treatment; Pregnant or nursing mothers Use (within the past 30 days) of: Illegal drugs (or if the urine drug screen is positive for tetrahydrocannabinol (THC), Cocaine, Amphetamine, Opiates, Methamphetamines, phencyclidine (PCP), Benzodiazepines, or Barbiturates), unless recent use of prescription Opiates or Benzodiazepines were taken for management of acute symptoms (e.g., tooth extraction, recent surgery); Experimental (investigational) drugs; Psychiatric medications including antidepressants (selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressant (TCAs), monoamine oxidase inhibitors (MAOIs), St. John's Wort), lithium, anti-psychotics or any other medications that are known to affect smoking cessation (e.g. clonidine); Phentermine, triptans, tryptophan, linezolid, dextromethorphan, opiates (unless taken for management of acute symptoms), tramadol, or dopamine agonists; Any agents that have documented correlation with increased incidence of valvulopathy and/or pulmonary hypertension (e.g., cyproheptadine, trazodone, nefazodone, amoxapine, tricyclic antidepressants, mirtazapine, pergolide, ergotamine, methysergide) (or anticipated use during the study); Wellbutrin, bupropion, Zyban, Chantix, varenicline, nicotine patch, nicotine replacement therapy or any other smoking cessation aid; Use of cigars, cigarillos, pipes, Hookah, dissolvable nicotine, snuff, chewing tobacco, or e-cigarettes Concurrent use of a serotonergic agent/combination associated with severe serotonin syndrome (within the past 30 days) Use of cigars, cigarillos, pipes, Hookah, dissolvable nicotine, snuff, chewing tobacco, or e-cigarettes within the past 30 days Self-report of consuming more than 6 alcoholic drinks on 1 or more days per week Significant adverse reaction to nicotine patch in the past Current participation or recent participation (in the past 30 days) in another smoking study at our Center or another research facility Current participation in another research study

Ages Eligible for Study
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Minimum Age: 18 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Nicotine e-cigs + Nicotine patches<br>Participants will receive e-cigarettes containing nicotine and nicotine patches (21mg/24hr) and will be asked to switch from cigarette use to use of the study e-cigarettes for eight weeks. | Drug: Nicotine patch<br>* Participants will wear the nicotine patch daily while switching from cigarette use to use of e-cigarettes for eight weeks.<br>* Other names: NicoDerm;Other: E-cigarettes<br>* Participants will use e-cigarettes containing nicotine while switching from cigarette use to use of e-cigarettes for eight weeks.<br>* Other names: electronic cigarettes;|
| Active Comparator: Non-nicotine e-cigs + Nicotine patches<br>Participants will receive e-cigarettes not containing nicotine and nicotine patches (21mg/24hr) and will be asked to switch from cigarette use to use of the study e-cigarettes for eight weeks. | Drug: Nicotine patch<br>* Participants will wear the nicotine patch daily while switching from cigarette use to use of e-cigarettes for eight weeks.<br>* Other names: NicoDerm;Other: Non-nicotine e-cigarettes<br>* Participants will use e-cigarettes not containing nicotine while switching from cigarette use to use of e-cigarettes for eight weeks.<br>* Other names: electronic cigarettes;|
| Active Comparator: Nicotine e-cigs + Placebo patches<br>Participants will receive e-cigarettes containing nicotine and placebo patches (21mg/24hr) and will be asked to switch from cigarette use to use of the study e-cigarettes for eight weeks. | Other: Placebo patch<br>* Participants will wear the placebo patch daily while switching from cigarette use to use of e-cigarettes for eight weeks.<br>Other: E-cigarettes<br>* Participants will use e-cigarettes containing nicotine while switching from cigarette use to use of e-cigarettes for eight weeks.<br>* Other names: electronic cigarettes;|
| Placebo Comparator: Non-nicotine e-cigs + Placebo patches<br>Participants will receive e-cigarettes not containing nicotine and placebo patches (21mg/24hr) and will be asked to switch from cigarette use to use of the study e-cigarettes for eight weeks. | Other: Placebo patch<br>* Participants will wear the placebo patch daily while switching from cigarette use to use of e-cigarettes for eight weeks.<br>Other: Non-nicotine e-cigarettes<br>* Participants will use e-cigarettes not containing nicotine while switching from cigarette use to use of e-cigarettes for eight weeks.<br>* Other names: electronic cigarettes;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Expired Air Carbon Monoxide (CO) to Assess Recent Smoking | The effects of e-cigarette nicotine content and patch nicotine content on the concurrent use of conventional cigarettes will be assessed by comparing the groups on the expired air carbon monoxide (CO) measured at the end of the exposure period (Week 8). | Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cigarette Use, Assessed by Self-report in Daily Dairies | The effects of e-cigarette nicotine content and patch nicotine content on the concurrent use of conventional cigarettes will be assessed by comparing the groups on self-report of cigarette consumption on daily diaries (for week 8 only, average cigarettes smoked per day). | Week 8 | 
| E-cigarette Use, Assessed by Self-report in Daily Dairies | The effects of e-cigarette nicotine content and patch nicotine content on the concurrent use of e-cigarettes will be assessed by comparing the groups on self-report of e-cigarette use on daily diaries (for week 8 only). | Week 8 | 
| Total Urinary 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) | The effects of e-cigarette nicotine content and patch nicotine content on the concurrent use of conventional cigarettes will be assessed by comparing the groups on total urinary NNAL, a metabolite of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), at the end of week 8. | Week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nicotine addiction, Cigarette smoking, Nicotine patches, E-cigarettes