Appeal of Nicotine Pouches Versus Cigarettes in the Ohio Appalachia Population

Study Overview
=================
Brief Summary
-----------------
This clinical trial estimates the abuse liability of nicotine pouches with varying nicotine concentrations relative to cigarette smoking in Appalachian, Ohio and Ohio smokers. Nicotine pouches are a novel tobacco product with potential to reduce or increase the harm of tobacco use. Evaluating nicotine pouches abuse liability among smokers in Ohio including the unique demographic of Appalachia may clarify the public health effect of NPs in Appalachian Ohio and across Ohio. Results may inform public health efforts, policy, and clinical care aimed at reducing tobacco-related disparities.

Detailed Description
-----------------
Aim 1: PRIMARY OBJECTIVE: I. To estimate the abuse liability of nicotine pouches (NPs) with varying nicotine concentrations relative to cigarette smoking. SECONDARY OBJECTIVE: I. To clarify the public health effect of NPs in Appalachian Ohio. EXPLORATORY OBJECTIVES: I. To estimate the abuse liability of NPs with varying nicotine concentrations relative to cigarette smoking by measuring nicotine pharmacokinetics. II. To estimate the abuse liability of NPs with varying nicotine concentrations relative to cigarette smoking by measuring subjective effects. III. To estimate the abuse liability of NPs with varying nicotine concentrations relative to cigarette smoking by measuring intentions to use and switch to NPs. OUTLINE: Patients are randomized to 1 of 3 arms. ARM I: Patients receive lower dose nicotine pouch orally (PO) over 30 minutes at visits 1, 2, and 3. ARM II: Patients receive higher dose nicotine pouch PO over 30 minutes at visits 1, 2, and 3. ARM III: Patients smoke usual brand of cigarettes, taking one puff every 30 seconds over 5 minutes at visits 1, 2, and 3. Aim 2: PRIMARY OBJECTIVE: I. To understand the pharmacokinetic difference between tobacco-derived and synthetic NPs. SECONDARY OBJECTIVE: I. To clarify the public health effect of NPs on adult smokers EXPLORATORY OBJECTIVES: I. To understand the differences in abuse liability between tobacco-derived and synthetic NPs by measuring nicotine pharmacokinetics. II. To understand the differences in abuse liability between tobacco-derived and synthetic NPs by measuring subjective effects. III. To estimate the abuse liability of tobacco-derived vs. synthetic NPs by measuring intentions to use and switch to NPs. OUTLINE: Patients are randomized to 1 of 3 arms. ARM I: Patients receive a 3mg dose nicotine pouch orally (PO) over 30 minutes at visits 1, 2, and 3. ARM II: Patients receive a 3mg dose nicotine pouch PO over 30 minutes at visits 1, 2, and 3. ARM III: Patients receive a 3mg dose nicotine pouch PO over 30 minutes at visits 1, 2, and 3.

Official Title
-----------------
Examining the Appeal of Nicotine Pouches in Ohio Appalachia

Conditions
-----------------
Cigarette Smoking-Related Carcinoma

Intervention / Treatment
-----------------
* Behavioral: Cigarette Smoking
* Drug: Nicotine Oral Pouch
* Drug: Nicotine Oral Pouch
* Other: Questionnaire Administration
* Drug: Nicotine Oral Pouch
* Drug: Nicotine Oral Pouch
* Drug: Nicotine Oral Pouch


Participation Criteria
=================
Eligibility Criteria
-----------------
Aim 1 Inclusion Criteria: Age 21 years or older. Reside in an Ohio Appalachian county. 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. Smoke at least 5 cigarettes per day for the past 30 days. Exclusion Criteria: Use tobacco products other than cigarettes >10 days per month. Use NP in the past 3 months. Unstable or significant psychiatric conditions (past and stable conditions will be allowed). Pregnant, planning to become pregnant, or breastfeeding. History of cardiac event or distress within the past 3 months. Currently attempting to quit all tobacco use. Self-reported diagnosis of lung disease including asthma (if uncontrolled or worse than usual), cystic fibrosis, or chronic obstructive pulmonary disease. Aim 2 Inclusion Criteria: Age 21 years or older. Reside in a Ohio. 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. Smoke at least 5 cigarettes per day for the past 30 days. Exclusion Criteria: Use tobacco products other than cigarettes >10 days per month. Use NP in the past 3 months. Unstable or significant psychiatric conditions (past and stable conditions will be allowed). Pregnant, planning to become pregnant, or breastfeeding. History of cardiac event or distress within the past 3 months. Currently attempting to quit all tobacco use. Self-reported diagnosis of lung disease including asthma (if uncontrolled or worse than usual), cystic fibrosis, or chronic obstructive pulmonary disease.

Ages Eligible for Study
-----------------
Minimum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aim 1: Arm I (lower dose nicotine pouch)<br>Patients receive lower dose nicotine pouch PO over 30 minutes at visits 1, 2, and 3. | Drug: Nicotine Oral Pouch<br>* Given lower dose nicotine pouch<br>* Other names: ZYN;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Experimental: Aim 1: Arm II (higher dose nicotine pouches)<br>Patients receive higher dose nicotine pouch PO over 30 minutes at visits 1, 2, and 3. | Drug: Nicotine Oral Pouch<br>* Given higher dose nicotine pouch<br>* Other names: ZYN;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Active Comparator: Aim 1: Arm III (cigarette smoking)<br>Patients smoke usual brand of cigarettes, taking one puff every 30 seconds over 5 minutes at visits 1, 2, and 3. | Behavioral: Cigarette Smoking<br>* Smoke preferred brand of cigarette<br>Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Experimental: Aim 2: Arm I (3mg NP)<br>Patients receive nicotine pouch PO over 30 minutes at visits 1, 2, and 3. | Other: Questionnaire Administration<br>* Ancillary studies<br>Drug: Nicotine Oral Pouch<br>* Given 3mg nicotine pouch (Aim 2)<br>* Other names: On!;|
| Experimental: Aim 2: Arm II (3mg NP)<br>Patients receive nicotine pouch PO over 30 minutes at visits 1, 2, and 3. | Other: Questionnaire Administration<br>* Ancillary studies<br>Drug: Nicotine Oral Pouch<br>* Given 3mg nicotine pouch (Aim 2)<br>* Other names: ZYN;|
| Experimental: Aim 2: Arm III (3mg NP)<br>Patients receive nicotine pouch PO over 30 minutes at visits 1, 2, and 3. | Other: Questionnaire Administration<br>* Ancillary studies<br>Drug: Nicotine Oral Pouch<br>* Given 3mg nicotine pouch (Aim 2)<br>* Other names: Fre;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate plasma nicotine concentration at t=30 minutes for each product. |  | Up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aim 1: Public health effect of NPs in Appalachian Ohio - if NPs can be used as a substitute for cigarette smoking | Data collected will show if NPs are a viable substitute for cigarette smoking. | Up to 6 months | 
| Evaluate plasma nicotine concentrations at t=5 through t=90 minutes |  | Up to 6 months | 
| Evaluate withdrawal relief at t=5 through t=90 minutes | We measure withdrawal relief using the Minnesota Withdrawal Scale (MNWS). We administer this questionnaire at each timepoint along the standardized scale of t=0, t=5, t=15, t=30, t=60 and t=90. The MNWS includes a minimum value of none and a maximum value or severe. The higher scores indicate increased withdrawal symptoms and lower scores indicate lessened or no withdrawal symptoms. | Up to 6 months | 
| Evaluate product appeal across all 3 products | Product appeal will be assessed using several scales, including the Modified E-Cigarette Smoking Questionnaire (mCEQ), the Product Evaluation Scale (PES), the Adapted Drug Effects Liking Scale, and the Study Product Effects Liking Scale which are administered after the final timepoint of each study visit. For both the mCEQ and PES, the minimum scale value is not at all and the maximum scale value is extremely. Higher scores can mean both better or worse depending on the question. Ex: Was using your smokeless tobacco satisfying? and Did using your smokeless tobacco make you nauseous? are both questions on each scale, so a higher score would vary in meaning based on the question. For the Adapted Drug Effects Liking and Study Product Effects Liking scales, minimum values include not at all and maximum value includes very pleasant. With the exception of one question on the Study Product Effects Liking Scale, a higher score indicates increased enjoyment of the product. | Up to 6 months |