Hookah Additive Research to Inform Product Standards

Study Overview
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Brief Summary
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This clinical trial evaluates how the content of waterpipe (WP) tobacco affects the appeal, puffing behavior, and toxicity of WP tobacco smoking. The data from the proposed study will provide direct links between WP tobacco's primary additives (sugars and humectants), CO and nicotine biomarkers, smoker preferences, perceptions of harm and puffing behaviors, and the subsequent range of toxicant exposures associated with these additives and behaviors. Study outcomes include waterpipe puffing behaviors, exhaled carbon monoxide levels, nicotine uptake, spirometry, sensory perceptions, smoking appeal, and risk perception. Waterpipe tobacco smoking is often the first combustible tobacco product tried by adolescents and young adults, possibly due to the widespread availability of heavily sweetened waterpipe tobacco and the perception that waterpipe smoking is a safer alternative to cigarette smoking. However, waterpipe tobacco smoking is associated with lung disease, carbon monoxide poisoning, and precursor conditions for oral and other cancers in adolescents and young adults. There is currently little data available on how the primary additives (by weight) in waterpipe tobacco affect puffing behaviors, toxicant exposures, pulmonary function and appeal. This clinical trial uses established waterpipe tobacco smokers, four investigational tobacco products with precisely manipulated levels of humectants and natural sugars in a single-blind, crossover (repeated measures) study design to determine how waterpipe tobacco additives effect human puffing behavior, nicotine uptake, flavor perceptions, lung function, and biomarkers of exposure.

Detailed Description
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Currently there are no regulations governing the content of WP tobacco. Because mandated changes in tobacco content may lead to unintended consequences that ultimately result in public health declines, human use behaviors must be well understood prior to implementing regulatory product standards. The proposed study will include preparing and characterizing the content of 4 investigational tobacco products (ITPs) (Aim 1); characterizing the mainstream smoke toxicant emissions from machine smoking the 4 ITPs using a single, established puffing regimen (Aim 2); measuring human puffing behavior, general harm and specific health risk and flavor perceptions, lung function, and biomarkers of exposure in a group of established WP smokers smoking the 4 ITPs in the laboratory (Aim 3), and estimating toxicant exposure ranges using machine smoking and puffing regimens derived from the human laboratory testing (Aim 4). The clinical trial (Aim 3) will focus on using a group of established adult and young adult WP smokers, a cross-over study design, CO and nicotine biomarkers, spirometry, cutting edge psychophysical measurement tools, and risk perception instruments to map the relationship between sensory experiences and preferences of sweetness and flavor to specific additive content in WP tobacco that affect these experiences, preferences, acute health effects, and toxicant exposures. Study subjects will participate in a series of 4 clinic sessions, each visit separated by at least a week, in which they smoke one of 4 tobacco preparations (single-blind) using a research grade waterpipe in a randomly assigned sequence in a smoking room with sufficiently controlled ventilation rate to keep ambient air CO levels below 25 ppm. Exhaled CO, whole blood samples and spirometry measures will be collected before and immediately after the smoking session. Taste perceptions, liking/disliking, and risk perceptions will be determined via questionnaires before, during, and after smoking.

Official Title
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Waterpipe Tobacco Additives and Their Effect on Human Puffing Behavior, Toxicant Exposures, Pulmonary Function, and Appeal

Conditions
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Tobacco-Related Carcinoma

Intervention / Treatment
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* Other: Questionnaire Administration
* Behavioral: Tobacco Smoking


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sufficient understanding of consent form and study procedures Age 21-50 years old Experienced WP smokers defined as having smoked a WP at least 3 times per month in the last month Willing/able to abstain from nicotine product use for at least 12 hours prior to the laboratory visits Willing to attend four laboratory sessions at the same time of day lasting approximately 3 hours (h) each Read and speak English Exclusion Criteria: Evident intoxication on any visit Exhaled breath CO > 10 ppm Pregnancy (known or suspected), trying to become pregnant, breastfeeding, unwillingness to use contraception for the duration of the study Significant smoking-related disease (by history) Any of the following in the past 30 days (self-report): Uncontrolled asthma or asthma that is worse than usual Severe respiratory allergies, such as wheezing, coughing, shortness of breath when exposed to known allergens Acute upper or lower respiratory illnesses like the flu, common cold, or pneumonia Any other serious lung infection or disease, such as tuberculosis, cystic fibrosis, or lung cancer Hospitalization for difficulty breathing Currently engaging in a WP tobacco smoking quit attempt

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 50 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: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tobacco flavor preparation; High Sweetness, High Humectant (tobacco smoking)<br>Participants smoke 1 of 4 waterpipe tobacco preparations over 45-60 minutes over 4 sessions, separated by at least 1 week. Questionnaires administered. | Other: Questionnaire Administration<br>* Ancillary studies<br>Behavioral: Tobacco Smoking<br>* Smoke waterpipe tobacco<br>* Other names: Tobacco, Smoking;|
| Experimental: Tobacco flavor preparation; High Sweetness, Medium Humectant (tobacco smoking)<br>Participants smoke 1 of 4 waterpipe tobacco preparations over 45-60 minutes over 4 sessions, separated by at least 1 week. Questionnaires administered. | Other: Questionnaire Administration<br>* Ancillary studies<br>Behavioral: Tobacco Smoking<br>* Smoke waterpipe tobacco<br>* Other names: Tobacco, Smoking;|
| Experimental: Tobacco flavor preparation; Medium Sweetness, High Humectant (tobacco smoking)<br>Participants smoke 1 of 4 waterpipe tobacco preparations over 45-60 minutes over 4 sessions, separated by at least 1 week. Questionnaires administered. | Other: Questionnaire Administration<br>* Ancillary studies<br>Behavioral: Tobacco Smoking<br>* Smoke waterpipe tobacco<br>* Other names: Tobacco, Smoking;|
| Experimental: Tobacco flavor preparation; Medium Sweetness, Medium Humectant (tobacco smoking)<br>Participants smoke 1 of 4 waterpipe tobacco preparations over 45-60 minutes over 4 sessions, separated by at least 1 week. Questionnaires administered. | Other: Questionnaire Administration<br>* Ancillary studies<br>Behavioral: Tobacco Smoking<br>* Smoke waterpipe tobacco<br>* Other names: Tobacco, Smoking;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Exhaled breath carbon monoxide (CO) | Assessing change from baseline (boost): collect before and immediately after each smoking session with a handheld electrochemical cell. Data will be analyzed using linear mixed models containing random subject effects. Since linear mixed models allow for incomplete data, data from all completed smoking sessions will be used in the analysis. Tukey's method will be used to adjust for multiple comparisons of the tobacco treatments. | Up to 2 years | 
| Change in Plasma nicotine boost | Assessing change from baseline (boost): Whole blood collected before and immediately after each smoking session, separated, and plasma layer transferred and stored at -80 °C until analysis for nicotine according to validated methods using LC-MS/MS. | Up to 2 years | 
| Change in Forced vital capacity (FVC) | Spirometer measurements will be collected. Data will be analyzed using linear mixed models containing random subject effects. Since linear mixed models allow for incomplete data, data from all completed smoking sessions will be used in the analysis. Tukey's method will be used to adjust for multiple comparisons of the tobacco treatments. | Up to 2 years | 
| Change in Forced expiratory volume in 1 second (FEV1) | Spirometer measurements will be collected. Data will be analyzed using linear mixed models containing random subject effects. Since linear mixed models allow for incomplete data, data from all completed smoking sessions will be used in the analysis. Tukey's method will be used to adjust for multiple comparisons of the tobacco treatments. | Up to 2 years | 
| Change in FEV1/FVC; The ratio of the forced expiratory volume in the first one second to the forced vital capacity of the lungs. | Spirometer measurements will be collected. Data will be analyzed using linear mixed models containing random subject effects. Since linear mixed models allow for incomplete data, data from all completed smoking sessions will be used in the analysis. Tukey's method will be used to adjust for multiple comparisons of the tobacco treatments. | Up to 2 years | 
| Change in Peak expiratory flow (PEF) | Spirometer measurements will be collected. Data will be analyzed using linear mixed models containing random subject effects. Since linear mixed models allow for incomplete data, data from all completed smoking sessions will be used in the analysis. Tukey's method will be used to adjust for multiple comparisons of the tobacco treatments. | Up to 2 years | 
| Change in Forced expiratory flow at 25-75% of FVC | Spirometer measurements will be collected. Data will be analyzed using linear mixed models containing random subject effects. Since linear mixed models allow for incomplete data, data from all completed smoking sessions will be used in the analysis. Tukey's method will be used to adjust for multiple comparisons of the tobacco treatments. | Up to 2 years | 
| Tobacco use history | Data will be analyzed using linear mixed models containing random subject effects. Since linear mixed models allow for incomplete data, data from all completed smoking sessions will be used in the analysis. Tukey's method will be used to adjust for multiple comparisons of the tobacco treatments. | Up to 2 years | 
| Nicotine dependence | Assessed by Hooked on Nicotine Checklist (HONC). 10 Yes or No questions, yes = 1, no = 0; minimum score = 0, maximum score = 10, higher scores mean greater nicotine dependence. Data will be analyzed using linear mixed models containing random subject effects. Since linear mixed models allow for incomplete data, data from all completed smoking sessions will be used in the analysis. Tukey's method will be used to adjust for multiple comparisons of the tobacco treatments. | Up to 2 years | 
| Nicotine dependence | Lebanese Waterpipe Dependence Scale (LWDS). Ten questions, min score = 0, max score = 36, higher sores mean greater nicotine dependence. Data will be analyzed using linear mixed models containing random subject effects. Since linear mixed models allow for incomplete data, data from all completed smoking sessions will be used in the analysis. Tukey's method will be used to adjust for multiple comparisons of the tobacco treatments. | Up to 2 years | 
| General harm and specific health risk perceptions | Assessed using harm/health risk perceptions questionnaire. Min scale = 0 (no harm), max scale = 10 (extreme harm). Higher scores mean greater perceived harm/health risk. Data will be analyzed using linear mixed models containing random subject effects. Since linear mixed models allow for incomplete data, data from all completed smoking sessions will be used in the analysis. Tukey's method will be used to adjust for multiple comparisons of the tobacco treatments. | Up to 2 years | 
| Subjective effects of smoking tobacco | Assessed using Direct Effects of Tobacco scale. Min scale = 0 (not at all), Max scale = extremely. Higher number total means tobacco has greater effect. Data will be analyzed using linear mixed models containing random subject effects. Since linear mixed models allow for incomplete data, data from all completed smoking sessions will be used in the analysis. Tukey's method will be used to adjust for multiple comparisons of the tobacco treatments. | Up to 2 years | 
| Change in Subjective effects of smoking tobacco | Assessed change from baseline using Direct Effects of Nicotine scale. Min scale = 0 (not at all), Max scale = 100 (extremely). Higher number means nicotine has greater effect. Data will be analyzed using linear mixed models containing random subject effects. Since linear mixed models allow for incomplete data, data from all completed smoking sessions will be used in the analysis. Tukey's method will be used to adjust for multiple comparisons of the tobacco treatments. | Up to 2 years | 
| Change in Subjective effects of smoking tobacco | Assessed change from baseline using Questionnaire for Urges to Smoke. Min scale: 1 (strongly disagree), Max scale = 6 (strongly agree). Higher number means greater urge to smoke. Data will be analyzed using linear mixed models containing random subject effects. Since linear mixed models allow for incomplete data, data from all completed smoking sessions will be used in the analysis. Tukey's method will be used to adjust for multiple comparisons of the tobacco treatments. | Up to 2 years | 
| Change in Nicotine withdrawal assessment | Assessed change from baseline using Waterpipe-modified Minnesota Withdrawal Scale. Min scale = 0 (not at all), Max scale = 100 (extremely). Higher number total means greater withdrawal symptoms. Data will be analyzed using linear mixed models containing random subject effects. Since linear mixed models allow for incomplete data, data from all completed smoking sessions will be used in the analysis. Tukey's method will be used to adjust for multiple comparisons of the tobacco treatments. | Up to 2 years | 
| Tobacco flavors perception, intensity of sweetness | To determine the relative intensity of specific flavors, e.g., sweetness, will use the general version of the Labeled Magnitude Scale (gLMS), to obtain data that would permit ratio comparisons of perceived sensation magnitudes. Min scale = 0, Max scale = 100. Higher number means perception is stronger. | Up to 2 years | 
| Tobacco flavors perception, degree of liking or disliking | To assess the degree of liking or disliking of flavors, will use the Labeled Hedonic Scale (LHS) to collect ratio-level data on the magnitude of liking and disliking of sensation. Min scale = 0, Max scale = 100. Higher number means greater liking. | Up to 2 years | 
| Puffing topography | Puff volume will be measured continuously during the smoking session using the research-grade waterpipe. Data will be analyzed using linear mixed models containing random subject effects. Since linear mixed models allow for incomplete data, data from all completed smoking sessions will be used in the analysis. Tukey's method will be used to adjust for multiple comparisons of the tobacco treatments. | Up to 2 years | 
| Puffing topography | Puff duration will be measured continuously during the smoking session using the research-grade waterpipe. Data will be analyzed using linear mixed models containing random subject effects. Since linear mixed models allow for incomplete data, data from all completed smoking sessions will be used in the analysis. Tukey's method will be used to adjust for multiple comparisons of the tobacco treatments. | Up to 2 years | 
| Puffing topography | Puff average flow rate will be measured continuously during the smoking session using the research-grade waterpipe. Data will be analyzed using linear mixed models containing random subject effects. Since linear mixed models allow for incomplete data, data from all completed smoking sessions will be used in the analysis. Tukey's method will be used to adjust for multiple comparisons of the tobacco treatments. | Up to 2 years | 
| Puffing topography | Puff peak flow rate will be measured continuously during the smoking session using the research-grade waterpipe. Data will be analyzed using linear mixed models containing random subject effects. Since linear mixed models allow for incomplete data, data from all completed smoking sessions will be used in the analysis. Tukey's method will be used to adjust for multiple comparisons of the tobacco treatments. | Up to 2 years | 
| Puffing topography | Interpuff interval will be measured continuously during the smoking session using the research-grade waterpipe. Data will be analyzed using linear mixed models containing random subject effects. Since linear mixed models allow for incomplete data, data from all completed smoking sessions will be used in the analysis. Tukey's method will be used to adjust for multiple comparisons of the tobacco treatments. | Up to 2 years |