Hookah Additive Research to Inform Product Standards

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

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05453773

Acronym

HARPS

Enrollment

Registered

2022-07-12

Start date

2022-06-19

Completion date

2023-05-11

Last updated

2024-12-31

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Tobacco-Related Carcinoma

Brief summary

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

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.

Interventions

OTHERQuestionnaire Administration

Ancillary studies

BEHAVIORALTobacco Smoking

Smoke waterpipe tobacco

Study design

Allocation

RANDOMIZED

Intervention model

FACTORIAL

Primary purpose

OTHER

Masking

SINGLE (Subject)

Eligibility

Sex/Gender

ALL

Age

21 Years to 50 Years

Healthy volunteers

Yes

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

Design outcomes

Primary

Measure	Time frame	Description
Change in Exhaled Breath Carbon Monoxide (CO)	Approximately 30 to 90 minutes	Change from baseline exhaled breath carbon monoxide (boost). CO was collected before and immediately after each smoking session with a handheld electrochemical cell.
Change in Plasma Nicotine	Approximately 30 to 90 minutes	Change from baseline plasma nicotine (boost): Whole blood was 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.
Change in Forced Vital Capacity (FVC)	Approximately 30 to 90 minutes	Spirometer measurements will be collected - change in forced vital capacity (FVC) (post-pre).
Change in Forced Expiratory Volume in 1 Second (FEV1)	Approximately 30 to 90 minutes	Spirometer measurements will be collected - change in forced expiratory volume in 1 second (FEV1) (post-pre)
Change in FEV1/FVC; The Ratio of the Forced Expiratory Volume in the First One Second to the Forced Vital Capacity of the Lungs.	Approximately 30 to 90 minutes	Spirometer measurements will be collected - change in FEV1/FVC, the ratio of the forced expiratory volume in the first one second to the forced vital capacity of the lungs (post-pre).
Change in Peak Expiratory Flow (PEF)	Approximately 30 to 90 minutes	Spirometer measurements will be collected - change in peak expiratory flow (PEF) (post-pre).
Change in Forced Expiratory Flow at 25-75% of FVC	Approximately 30 to 90 minutes	Spirometer measurements will be collected - change in forced expiratory flow at 25-75% of FVC (post-pre).
Tobacco Use History	Baseline	Ever use of tobacco products, assessed at the first study visit
Nicotine Dependence (HONC)	Baseline	Hooked on Nicotine Checklist (HONC) comprised of 10 Yes or No questions, assessed on the first study visit. Scores range from 0 to 10 with higher scores indicating greater nicotine dependence.
Nicotine Dependence (LWDS)	Baseline	Lebanese Waterpipe Dependence Scale (LWDS) comprised of twelve questions and assessed on the first study visit. LWDS values range from 0 to 36 where higher sores indicate greater nicotine dependence.
General Harm and Health Risk Perceptions	Post Smoking Session	Assessed using harm/health risk perceptions questionnaire. General harm is rated after the smoking session on a scale from 0 (no harm) to 10 (extreme harm) with higher scores indicating a greater perceived harm/health risk.
Subjective Effects of Smoking Tobacco	Post Smoking Session	Direct Effects of Tobacco scale; the scale for each effect ranges from 0 (not at all) to 100 (extremely) with higher ratings indicating a greater effect of the tobacco.
Change in Subjective Effects of Smoking Tobacco - Direct Effects of Nicotine	Approximately 30 to 90 minutes	Change in Direct Effects of Nicotine scale from baseline (post - pre). The scale for each effect ranges from 0 (not at all) to 100 (extremely) with higher ratings indicating a greater effect of the tobacco.
Change in Subjective Effects of Smoking Tobacco (QSU)	Approximately 30 to 90 minutes	Change from baseline Questionnaire for Urges to Smoke (post - pre). This is a 10-item measure where participants rate smoking-related items on a 6-point Likert scale ranging from 1 (strongly disagree) to 6 (strongly agree). Items are collapsed into two previously identified factors (Factor 1: strong desire and intention to smoke; Factor 2: anticipation of relief from withdrawal symptoms). Scores are calculated by summing the items and range from 5 to 30 with higher scores indicating greater urge to smoke.
Change in Nicotine Withdrawal Assessment (MNWS)	Approximately 30 to 90 minutes	Change from baseline using Waterpipe-modified Minnesota Withdrawal Scale (post - pre). The scale ranges from 0 (not at all) to 100 (extremely) with higher total numbers meaning greater withdrawal symptoms.
Tobacco Flavor Perception (gLMS)	Post Smoking Session	To determine the relative intensity of specific flavors, e.g., sweetness, the general version of the Labeled Magnitude Scale (gLMS) was used post-smoking session. The scale ranges from 0 to 100 where higher scores indicate that the perception is stronger.
Tobacco Flavors Perception, Degree of Liking or Disliking (LHS)	Post Smoking Session	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 post-smoking session. Scores range from 0 to 100 with higher scores indicating greater liking.
Puffing Topography - Puff Volume	Up to 60 minutes	Puff volume measured continuously during the smoking session using the research-grade waterpipe.
Puffing Topography - Puff Duration	Up to 60 minutes	Puff duration measured continuously during the smoking session using the research-grade waterpipe.
Puffing Topography - Flow Rate	Up to 60 minutes	Puffing average flow rate measured continuously during the smoking session using the research-grade waterpipe.
Puffing Topography - Peak Flow Rate	Up to 60 minutes	Puffing peak flow rate measured continuously during the smoking session using the research-grade waterpipe.
Puffing Topography - Interpuff Interval	Up to 60 minutes	Interpuff interval measured continuously during the smoking session using the research-grade waterpipe.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Overall Population Population of randomized participants who fully completed at least one study visit	51
Total	51

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Difficult Blood Draw	3
Overall Study	Lost to Follow-up	3
Overall Study	Withdrawal by Subject	3

Baseline characteristics

Characteristic	Overall Population
Age, Continuous	27.55 years STANDARD_DEVIATION 4.27
Age when first tried Waterpipe	18.69 years STANDARD_DEVIATION 4.47
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	7 Participants
Race (NIH/OMB) Black or African American	19 Participants
Race (NIH/OMB) More than one race	2 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants
Race (NIH/OMB) White	18 Participants
Sex: Female, Male Female	23 Participants
Sex: Female, Male Male	28 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	0 / 47	0 / 46	0 / 46	0 / 48
other Total, other adverse events	0 / 47	0 / 46	0 / 46	0 / 48
serious Total, serious adverse events	0 / 47	0 / 46	0 / 46	0 / 48

Outcome results

Primary

Change in Exhaled Breath Carbon Monoxide (CO)

Change from baseline exhaled breath carbon monoxide (boost). CO was collected before and immediately after each smoking session with a handheld electrochemical cell.