Examining the Impact of Nicotine Pouches in Rural Ohio and Ohio Appalachia

Study Overview
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Brief Summary
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This clinical trial examines the impact of nicotine patches on preventing cancer in rural and Appalachia Ohio residents. Nicotine pouches are new smokeless tobacco products that are marketed as substitutes for smokeless tobacco and are gaining in popularity. There is little research on how nicotine pouches will be adopted by residents of Ohio Appalachia and rural Ohio. This study may help researchers better understand the appeal and potential impact of nicotine pouches on public health.

Detailed Description
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PRIMARY OBJECTIVES: I. Assess appeal, perceived substitutability, and nicotine delivery of nicotine pouches (NPs) with high versus (vs.) low free-base nicotine (FBN) content among rural and Appalachian moist snuff users. II. Evaluate whether smokeless tobacco (SLT) dependence modifies effects of NP FBN content on product appeal, perceived substitutability, and nicotine delivery. OUTLINE: Participants are randomized to 1 of 6 arms. ARM I: Participants receive their usual brand of smokeless tobacco at study visit 1, ZYN brand nicotine pouch at study visit 2, and Rogue brand nicotine pouch at study visit 3. Participants also undergo intravenous (IV) line insertion and collection of blood on study. ARM II: Participants receive their usual brand of smokeless tobacco at study visit 1, Rogue brand nicotine pouch at study visit 2, and ZYN brand nicotine pouch at study visit 3. Participants also undergo IV line insertion and collection of blood on study. ARM III: Participants receive ZYN brand nicotine pouch at study visit 1, their usual brand of smokeless tobacco at study visit 2, and Rogue brand nicotine pouch at study visit 3. Participants also undergo IV line insertion and collection of blood on study. ARM IV: Participants receive ZYN brand nicotine pouch at study visit 1, Rogue brand nicotine pouch at study visit 2, and their usual brand of smokeless tobacco at study visit 3. Participants also undergo IV line insertion and collection of blood on study. ARM V: Participants receive Rogue brand nicotine patch at study visit 1, their usual brand of smokeless tobacco at study visit 2, and ZYN brand nicotine patch at study visit 3. Participants also undergo IV line insertion and collection of blood on study. ARM VI: Participants receive Rogue brand nicotine pouch at study visit 1, ZYN brand nicotine pouch at study visit 2, and their usual brand of smokeless tobacco at study visit 3. Participants also undergo IV line insertion and collection of blood on study.

Official Title
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Examining the Impact of Nicotine Pouches in Rural Ohio and Ohio Appalachia

Conditions
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Tobacco-Related Carcinoma

Intervention / Treatment
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* Procedure: Biospecimen Collection
* Drug: Nicotine Oral Pouch
* Drug: Nicotine Oral Pouch
* Other: Questionnaire Administration
* Drug: Smokeless Tobacco


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 21 years or older Reside in an Ohio Appalachian county or surrounding rural area Willing to complete study procedures, including abstaining from all tobacco, nicotine, and marijuana for 12 hours before clinic visits Ability to read and speak English Daily use of smokeless tobacco for the past 3 months Exclusion Criteria: Use tobacco products other than smokeless tobacco > 10 days per month Unstable or significant psychiatric conditions for > 1 year (past and stable conditions will be allowed) Pregnant, planning to become pregnant, or breastfeeding History of cardiac event or distress, including but not limited to uncontrolled high blood pressure, chest pain, significant oral lesions, throat, mouth, or other oral cancer, and shortness of breath within the past 1 year Working with a cessation counselor, using cessation devices such as Chantix or Wellbutrin, or planning to quit within the next 3 months Self-reported diagnosis of lung disease including asthma (if uncontrolled or worse than usual), cystic fibrosis, throat, tongue, or other oral cancer, lung cancer, or chronic obstructive pulmonary disease

Ages Eligible for Study
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Minimum Age: 21 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: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (usual SLT, ZYN NP, Rogue NP)<br>Participants receive their usual brand of smokeless tobacco at study visit 1, ZYN brand nicotine patch at study visit 2, and Rogue brand nicotine patch at study visit 3. Participants also undergo IV line insertion and collection of blood on study. | Procedure: Biospecimen Collection<br>* Undergo collection of blood<br>* Other names: Specimen Collection;Drug: Nicotine Oral Pouch<br>* Receive ZYN brand NP<br>* Other names: ZYN;Drug: Nicotine Oral Pouch<br>* Receive Rogue brand NP<br>* Other names: Rogue;Other: Questionnaire Administration<br>* Ancillary studies<br>Drug: Smokeless Tobacco<br>* Receive usual SLT<br>* Other names: Smoking, Tobacco and Cancer - Smokeless Tobacco;|
| Experimental: Arm II (usual SLT, Rogue NP, ZYN NP)<br>Participants receive their usual brand of smokeless tobacco at study visit 1, Rogue brand nicotine patch at study visit 2, and ZYN brand nicotine patch at study visit 3. Participants also undergo IV line insertion and collection of blood on study. | Procedure: Biospecimen Collection<br>* Undergo collection of blood<br>* Other names: Specimen Collection;Drug: Nicotine Oral Pouch<br>* Receive ZYN brand NP<br>* Other names: ZYN;Drug: Nicotine Oral Pouch<br>* Receive Rogue brand NP<br>* Other names: Rogue;Other: Questionnaire Administration<br>* Ancillary studies<br>Drug: Smokeless Tobacco<br>* Receive usual SLT<br>* Other names: Smoking, Tobacco and Cancer - Smokeless Tobacco;|
| Experimental: Arm III (ZYN NP, usual SLT, Rogue NP)<br>Participants receive ZYN brand nicotine patch at study visit 1, their usual brand of smokeless tobacco at study visit 2, and Rogue brand nicotine patch at study visit 3. Participants also undergo IV line insertion and collection of blood on study. | Procedure: Biospecimen Collection<br>* Undergo collection of blood<br>* Other names: Specimen Collection;Drug: Nicotine Oral Pouch<br>* Receive ZYN brand NP<br>* Other names: ZYN;Drug: Nicotine Oral Pouch<br>* Receive Rogue brand NP<br>* Other names: Rogue;Other: Questionnaire Administration<br>* Ancillary studies<br>Drug: Smokeless Tobacco<br>* Receive usual SLT<br>* Other names: Smoking, Tobacco and Cancer - Smokeless Tobacco;|
| Experimental: Arm IV (ZYN NP, Rogue NP, usual SLT)<br>Participants receive ZYN brand nicotine patch at study visit 1, Rogue brand nicotine patch at study visit 2, and their usual brand of smokeless tobacco at study visit 3. Participants also undergo IV line insertion and collection of blood on study. | Procedure: Biospecimen Collection<br>* Undergo collection of blood<br>* Other names: Specimen Collection;Drug: Nicotine Oral Pouch<br>* Receive ZYN brand NP<br>* Other names: ZYN;Drug: Nicotine Oral Pouch<br>* Receive Rogue brand NP<br>* Other names: Rogue;Other: Questionnaire Administration<br>* Ancillary studies<br>Drug: Smokeless Tobacco<br>* Receive usual SLT<br>* Other names: Smoking, Tobacco and Cancer - Smokeless Tobacco;|
| Experimental: Arm V (Rogue NP, usual SLT, ZYN NP)<br>Participants receive Rogue brand nicotine patch at study visit 1, their usual brand of smokeless tobacco at study visit 2, and ZYN brand nicotine patch at study visit 3. Participants also undergo IV line insertion and collection of blood on study. | Procedure: Biospecimen Collection<br>* Undergo collection of blood<br>* Other names: Specimen Collection;Drug: Nicotine Oral Pouch<br>* Receive ZYN brand NP<br>* Other names: ZYN;Drug: Nicotine Oral Pouch<br>* Receive Rogue brand NP<br>* Other names: Rogue;Other: Questionnaire Administration<br>* Ancillary studies<br>Drug: Smokeless Tobacco<br>* Receive usual SLT<br>* Other names: Smoking, Tobacco and Cancer - Smokeless Tobacco;|
| Experimental: Arm VI (Rogue NP, ZYN NP, usual SLT)<br>Participants receive Rogue brand nicotine patch at study visit 1, ZYN brand nicotine patch at study visit 2, and their usual brand of smokeless tobacco at study visit 3. Participants also undergo IV line insertion and collection of blood on study | Procedure: Biospecimen Collection<br>* Undergo collection of blood<br>* Other names: Specimen Collection;Drug: Nicotine Oral Pouch<br>* Receive ZYN brand NP<br>* Other names: ZYN;Drug: Nicotine Oral Pouch<br>* Receive Rogue brand NP<br>* Other names: Rogue;Other: Questionnaire Administration<br>* Ancillary studies<br>Drug: Smokeless Tobacco<br>* Receive usual SLT<br>* Other names: Smoking, Tobacco and Cancer - Smokeless Tobacco;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma nicotine delivery (Aim 1) | Will use linear or logistic mixed effects regression models as appropriate (with a random subject effect) to assess the effects of product type on plasma nicotine delivery. Model assumptions will be checked, and variables will be transformed as needed. Missing data will not be imputed as likelihood based linear mixed models will yield valid inference under missing at random assumptions. Calculated power to detect differences in maximum nicotine concentration using repeated measures ANOVA. | From baseline to study completion, assessed up to 2 years | 
| Behavioral intentions (Aim 1) | Will use linear or logistic mixed effects regression models as appropriate (with a random subject effect) to assess behavioral intentions with regard to nicotine pouches (NPs). Model assumptions will be checked, and variables will be transformed as needed. Missing data will not be imputed as likelihood based linear mixed models will yield valid inference under missing at random assumptions. Calculated power to detect differences in maximum nicotine concentration using repeated measures ANOVA. | From baseline to study completion, assessed up to 2 years | 
| Baseline characteristics (Aim 1) | Will use linear or logistic mixed effects regression models as appropriate (with a random subject effect) to control for baseline characteristics found to be associated with the outcome. Model assumptions will be checked, and variables will be transformed as needed. Missing data will not be imputed as likelihood based linear mixed models will yield valid inference under missing at random assumptions. Calculated power to detect differences in maximum nicotine concentration using repeated measures ANOVA. | From baseline to study completion, assessed up to 2 years | 
| Smokeless tobacco (SLT) type and behavioral intentions (Aim 2) | Will use linear or logistic mixed effects regression models as appropriate to assess the effects of product type on behavioral intentions. Statistical significance of the interaction terms will be determined using Wald tests. Models will additionally control for baseline characteristics found to be associated with the outcome. Model assumptions will be checked, and variables will be transformed as needed. Missing data will not be imputed as likelihood based linear mixed models will yield valid inference under missing at random assumptions. Calculated power to detect differences in maximum nicotine concentration using repeated measures ANOVA. | From baseline to study completion, assessed up to 2 years | 
| Smokeless tobacco (SLT) dependence effects on NP free-base nicotine (FBN) content on product appeal (Aim 2) | Will use linear or logistic mixed effects regression models as appropriate to assess the effects of product type between the two-level indicator for SLT dependence (low/moderate vs. high). Statistical significance of the interaction terms will be determined using Wald tests. Models will additionally control for baseline characteristics found to be associated with the outcome. Model assumptions will be checked, and variables will be transformed as needed. Missing data will not be imputed as likelihood based linear mixed models will yield valid inference under missing at random assumptions. Calculated power to detect differences in maximum nicotine concentration using repeated measures ANOVA. | From baseline to study completion, assessed up to 2 years |