A Study of Unfiltered Cigarettes Among Committed Smokers

Study Overview
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Brief Summary
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This study is an open-label, randomized, 9-week, two-sequence, two-treatment, cross-over clinical trial of 40 adult filtered cigarette smokers who switch to unfiltered cigarettes There will be a 1-week baseline period, 2 weeks of smoking filtered or unfiltered cigarettes (determined at time of randomization), and a 3-week washout period, followed by post-washout baseline week, and a crossover to 2 weeks of smoking the opposite condition.

Detailed Description
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This innovative research project will assess the acceptability among committed smokers of switching to unfiltered cigarettes from filtered cigarettes and compare the measurement of exposure to nicotine and carcinogens after such a switch from filtered to unfiltered cigarettes. Such research will inform regulatory policy regarding the possibility of banning filters from the U.S. cigarette market. This high-impact pilot project is a randomized, cross-over clinical trial among smokers to measure changes in their puffing behavior, carcinogen exposures, nicotine exposure, and attitudes toward smoking unfiltered cigarettes if they were to no longer able to buy filtered cigarettes. The overall objective for this pilot trial is to collect preliminary data to inform design of a larger clinical trial in assessing changes in attitudes toward smoking unfiltered cigarettes; smoking topography; and urinary cotinine, urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and volatile organic compound (VOC) excretion resulting from switching from filtered to unfiltered cigarettes among a sample of committed smokers. Aim 1. Determine smokers' satisfaction, and attitudes towards smoking cigarettes if they were to switch from smoking filtered to unfiltered cigarettes. The investigators hypothesize that smokers who smoke unfiltered cigarettes will have less satisfaction with their smoking compared with smoking filtered cigarettes. Aim 2. Measure changes in smoking topography and cigarettes smoked per day among smokers who change to unfiltered cigarettes for two weeks compared with these measures while smoking filtered cigarettes. The investigators hypothesize that smokers who smoke unfiltered cigarettes for two weeks will change their topography such that they will inhale less deeply and frequently and will smoke fewer cigarettes per day. Aim 3. Measure changes in urinary cotinine, NNAL, and VOC excretion among smokers who smoke unfiltered cigarettes for two weeks compared to smoking filtered cigarettes. The investigators hypothesize that smokers who smoke unfiltered cigarettes for two weeks will have lower urinary cotinine, NNAL, and VOC excretion compared with filtered cigarettes. The results from this trial can inform a larger clinical trial that can be submitted to the National Institutes of Health/Food and Drug Administration to develop evidence on the potentially positive impact of removing plastic filters from commercial cigarettes. It will allow us to develop sound scientific methods to assess the topography of smoking and excretion of cotinine, tobacco-specific nitrosamines, and VOCs by smokers who smoke cigarettes with and without filters. This new knowledge may lead the Food and Drug Administration or specific states to consider banning the sale of filtered cigarettes because filters make it easier for young people to start smoking, unjustifiably discourage smokers from quitting, and contaminate the environment with non-biodegradable, toxic waste.

Official Title
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A Randomized Cross-over Clinical Trial of Unfiltered Cigarettes

Conditions
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Cigarette Smoking, Tobacco Smoking

Intervention / Treatment
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* Other: Unfiltered Cigarettes
* Other: Filtered Cigarettes


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Are non-institutionalized, and Able to provide informed consent, and Are ages 21 to 65, and Smoke at least 25 days per month, and Smoke at least 5 cigarettes per day on the days they smoke, and Have been smoking cigarettes for at least 1 year, and Have smoked exclusively Camel or Pall Mall cigarettes over the past two weeks, or are willing to do so for the two weeks prior to, and for seven weeks during, the study, and Are fluent in English, and Have regular access to a telephone, and Have smoked only filtered cigarettes for the past year, and Have access to transportation to California State University, San Marcos (CSUSM), and Report primary (≥50% of the time) smoking of cigarettes, allowing for secondary use of other tobacco products, and Agree to the terms of the trial Exclusion Criteria: Do not meet one or more of the above inclusion criteria, or Self-report uncontrolled diabetes (i.e., diagnosed with diabetes, and it is not being managed by a physician), or Present to the enrollment visit with a systolic blood pressure greater than 160 mm Hg or a diastolic blood pressure greater than 105 mm Hg, or Self-report involvement in another clinical trial, or Self-report hospitalization for psychiatric issues or had a heart-related event (e.g. heart attack) at enrollment or within the past 30 days, or Self-report attempts to quit or cut down on smoking in past 30 days, or Self-report use of pharmacotherapy to aid smoking cessation within the past 30 days, or Are breastfeeding, pregnant, or may become pregnant during the next six months, or Are planning to move out of San Diego in the next 9 weeks, or Do not meet expected expired carbon monoxide (CO) measurements of smokers (Expired CO measurements>10 parts per million (ppm) will confirm status as a current smoker of at >5 cigarettes/day on the initial visit), or Are deemed mentally unstable (i.e., psychotic, under influence of drugs or alcohol, or unable to comprehend the call or meeting) or physically unfit (i.e, physically unwell) to participate in the study based on the researcher's determination at the enrollment visit

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Participants receive one of two alternative interventions during the initial phase of the study and receive the other intervention during the second phase of the study.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Study Group 1<br>Study Group 1 will begin the first treatment period with the provided Unfiltered Cigarettes intervention for two weeks, followed by a three-week wash-out period, before switching to the provided Filtered Cigarette intervention for two weeks. | Other: Unfiltered Cigarettes<br>* Participants will be given unfiltered Pall Mall or Camel cigarettes to smoke for two weeks according to the brand they smoked prior to the start of the study. They will agree to smoke the cigarettes using a monitoring device (CReSS) that measures puffing behavior on five (5) days during each of the two weeks. They will also collect their cigarette butts on all days as a measure of smoking behaviors.<br>Other: Filtered Cigarettes<br>* Participants will be given filtered Pall Mall or Camel cigarettes to smoke for two weeks according to the brand they smoked prior to the start of the study. They will agree to smoke the cigarettes using a monitoring device (CReSS) that measures puffing behavior on five (5) days during each of the two weeks. They will also collect their cigarette butts on all days as a measure of smoking behaviors.<br>|
| Experimental: Study Group 2<br>Study Group 2 will begin the first treatment period with the provided Filtered Cigarettes intervention for two weeks, followed by a three-week wash-out period, before switching to the provided Unfiltered Cigarette intervention for two weeks. | Other: Unfiltered Cigarettes<br>* Participants will be given unfiltered Pall Mall or Camel cigarettes to smoke for two weeks according to the brand they smoked prior to the start of the study. They will agree to smoke the cigarettes using a monitoring device (CReSS) that measures puffing behavior on five (5) days during each of the two weeks. They will also collect their cigarette butts on all days as a measure of smoking behaviors.<br>Other: Filtered Cigarettes<br>* Participants will be given filtered Pall Mall or Camel cigarettes to smoke for two weeks according to the brand they smoked prior to the start of the study. They will agree to smoke the cigarettes using a monitoring device (CReSS) that measures puffing behavior on five (5) days during each of the two weeks. They will also collect their cigarette butts on all days as a measure of smoking behaviors.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in mean flow rate (mL/s) | Mean flow rate, in mL per second, measures the flow of air through the CReSS as participants smoke cigarettes. | 9 weeks | 
| Change in number of puffs per cigarette | Measured by the CReSS device as participants smoke cigarettes | 9 weeks | 
| Change in duration of each cigarette puff (in seconds) | Measured by the CReSS device as participants smoke cigarettes | 9 weeks | 
| Change in inter-puff interval in seconds | The time between puffs on the cigarette, measured by the CReSS device as participants smoke cigarettes | 9 weeks | 
| Change in volume of each puff (mL) | Measured by the CReSS device as participants smoke cigarettes | 9 weeks | 
| Change in total smoke intake (mL) | Measured by the CReSS device as participants smoke cigarettes | 9 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary biomarker measurements | Target analytes are creatinine (the main proximate metabolite of nicotine), total (free + conjugated) 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (tNNAL, a carcinogenic tobacco-specific n-nitrosamine metabolite specific to tobacco smoke exposure), and a set of eight volatile organic compounds (VOCs, potentially toxic by-products of tobacco combustion). VOC concentrations will be measured at baseline in this study to account for possible additional sources of VOC exposure (assuming subjects' additional exposure remains consistent). VOCs will be measured as their urinary metabolites; i.e., mercapturic acid derivatives. The target parent VOCs are ethylene oxide, 1,3 butadiene, crotonaldehyde, acrolein, benzene, acrylamide, acrylonitrile, and propylene oxide. The biomarkers' urine concentration will be normalized to creatinine. Baseline midstream urine samples of at least 30 mL will be collected at baseline, post-washout, and at the end of each study cigarette period. | 9 weeks | 
| Cigarette satisfaction: mCEQ | Satisfaction with test cigarettes will be assessed using the 12-item modified Cigarette Evaluation Scale (mCEQ). This validated tool uses visual analog scales to assess subjective ratings: general acceptability (bad to very good), smoking need (not at all to very strong), smoking satisfaction (not at all to very good), harshness (not at all to very strong) and pleasantness of smoke taste (not tasty at all to very tasty). Open-ended questions will also be asked regarding subject's experience smoking unfiltered cigarettes. | 9 weeks | 
| Change in answers to Stanford Perceptions Survey of Youth questions | Qualitative questions assessing knowledge abut cigarette filters, behaviors if filtered cigarettes were no longer available, and support for policy related to filtered cigarettes. | 9 weeks | 
| Change in perceptions of cigarette harshness | As measured by a visual analog scale of 0 (not harsh at all) to 100 (extremely harsh) | 9 weeks | 
| Change in perceptions of cigarette draw | As measured by a visual analog scale of 0 (very hard to draw smoke) to 100 (very easy to draw smoke) | 9 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cigarette filters, Cigarette smoking, Unfiltered cigarettes