Methods Project 4: Clinical Trial - Amended

Study Overview
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Brief Summary
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Cigarette smokers will be randomized to E-cigarette, Nicotine Gum or Lozenge, or Control Group. Participants will enter a 1 week sampling phase. Smokers interested in continuing with the study after the sampling phase will undergo a 2 week baseline assessment phase and will then enter an 8 week intervention. Tobacco use patterns, subjective responses to product, and nicotine and toxicant exposure will be assessed.

Detailed Description
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Sampling period (1 week): Subjects will be randomized to an alternative nicotine product (E-cigarette, Nicotine Gum or Lozenge) or assigned to continue smoking their usual brand cigarettes. Subjects will complete screening assessments, asked to sample the assigned product and start recording their cigarette or other tobacco intake on a daily basis using an interactive voice response system (IVR). Smokers assigned to the control condition (smoking usual brand cigarettes) will be asked to choose the product that they would like to sample. Baseline smoking period: After sampling, subjects who meet specific criteria will continue with the experimental intervention phase. These subjects will be required to attend 2 baseline clinic visits where baseline assessments will be captured. Records of their cigarette or other tobacco intake on a daily basis will continue using the interactive voice response system (IVR). Experimental Period: After the baseline assessment, subjects will be instructed to either partially or completely substitute their cigarette smoking with their assigned product. They will assigned to one of six experimental conditions: smoking usual brand cigarette controls, who after 8-weeks will be offered any of the other nicotine products to use as they choose for 8 weeks; complete substitution (i.e., no smoking) with an E-cigarette; partial substitution with an E-cigarette; complete substitution (i.e., no smoking) with nicotine gum or nicotine lozenge. The assigned product, E-cigarette, Nic Gum or Lozenge, but not usual brand cigarettes, will be provided to subjects at the clinic visits. Subjects will attend clinic visits over the next 8 weeks where tobacco use patterns and biomarker data will be collected.

Official Title
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Project 4: Clinical Trial Method for Assessing a Tobacco Product Part of Models for Tobacco Product Evaluation:

Conditions
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Tobacco Smoking

Intervention / Treatment
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* Other: Cigarettes
* Other: E-Cigarette
* Other: Nicotine Gum or Lozenge


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects who are at least 18 years of age; Daily smoker; Generally good health; Subject has provided written informed consent to participate in the study (adolescents under the age of 18 will be excluded because this project involves continued use of tobacco products and new tobacco products); Exclusion Criteria: Unstable health; Pregnant or breastfeeding (due to toxic effects from tobacco products); Unable to read for comprehension or completion of study documents.

Ages Eligible for Study
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Minimum Age: 18 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Usual Brand Cigarette<br>Smoking usual brand cigarette controls, who after 8-weeks will be offered alternative nicotine products and instructed for partial or complete substitution of cigarettes (subject's choice); | Other: Cigarettes<br>* Smoke their usual brand of cigarettes and follow their normal patterns of use.<br>|
| Experimental: Complete Substitution E-Cigarette<br>Complete substitution (i.e., no smoking) with e-cigarette use | Other: E-Cigarette<br>* Use of E-cigarette: multiple flavors offered.<br>|
| Experimental: Partial Substitution E-Cigarette<br>Partial substitution, encouraged to use e-cigarettes instead of smoking usual cigarettes | Other: Cigarettes<br>* Smoke their usual brand of cigarettes and follow their normal patterns of use.<br>Other: E-Cigarette<br>* Use of E-cigarette: multiple flavors offered.<br>|
| Experimental: Complete Substitution Nic Gum or Lozenge<br>Complete substitution (i.e., no smoking) to nicotine gum or lozenge use | Other: Nicotine Gum or Lozenge<br>* Subject choice: Use of nicotine gum or nicotine lozenge, multiple flavors offered<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare total nicotine equivalents (TNE) based on differing instructions for oral tobacco, nicotine replacement or e-cigarette use. | Compare the exposure to nicotine in the two instructions for use arms (complete substitution vs. partial substitution) across study products and compared to medicinal nicotine products and usual brand cigarettes. | 6 months | 
| Determine stabilization of product use (e.g., cigarette, oral tobacco, e-cigarette or medicinal nicotine patterns of use). | Examining time effects for patterns of use of cigarettes, nicotine replacement, oral tobacco or e-cigarette. | 6 months | 
| Consumer perception of the product and response to the product after sampling. | Consumer perception of the product evidenced by choice of which product to use in the trial after sampling. | 6 months | 
| Compare NNK exposure based on differing instructions for oral tobacco, nicotine replacement or e-cigarette use. | Complete substitution vs. partial substitution of study products for cigarettes and compare the exposure to NNK by analyzing NNAL levels in subject urine. These products are compared to medicinal nicotine products and usual brand cigarettes. | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cigarette, smoking, e-cigarette, nicotine replacement therapy, nrt, tobacco