Controlled Exposure of Healthy Nonsmokers to Secondhand and Thirdhand Cigarette Smoke (THS04)

Controlled Human Exposure and THS Generation Core

This study compares the health effects of dermal and inhalational exposure to thirdhand cigarette smoke to those of inhalational exposure to secondhand cigarette smoke in healthy, adult nonsmokers. Our hypothesis is that dermal exposure increases exposure to the tobacco specific carcinogen, NNK and may affect both endothelial function and epidermal integrity.

Study Overview

• Status: Suspended
• Conditions: Pollution; Exposure; Exposure to Pollution; Smoke Inhalation
• Intervention / Treatment: Other: Cigarette Smoke; Other: Clean Air and Clean Clothing/Sham exposure

Detailed Description

Thirdhand cigarette smoke is the smoke chemicals that persist in the environment after smoking. Indoors, they can be found both on surfaces and in the air. Thirdhand smoke derives from secondhand smoke and contains the chemicals that stick to surfaces, are re-emitted into the air and that form by chemical reactions both on surfaces and in the air.

Thirdhand smoke can contain higher concentrations of the tobacco-specific nitrosamine and known carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) than secondhand smoke, because nicotine reacts to form NNK in the indoor environment. Dermal exposure to thirdhand smoke includes nicotine, NNK and other tobacco-specific nitrosamines, polycyclic aromatic hydrocarbons, and volatile organic compounds. Inhalational exposure to thirdhand smoke includes nicotine, ultrafine particles and volatile organic compounds. Previous studies have shown that inhalational exposure to secondhand cigarette smoke causes endothelial dysfunction, which is a risk factor for heart disease and heart attacks.

• Study Type: Interventional
• Enrollment (Estimated): 66
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Suzaynn F Schick, PhD; Phone Number: 628-206-5904; Email: suzaynn.schick@ucsf.edu
• Study Contact Backup: Name: Abel Huang, BA; Phone Number: 415-6286685; Email: abel.huang@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94110
      • Zuckerberg San Francisco General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy on the basis of medical history, blood pressure and test of C-reactive protein, lipids and blood sugar.
• Non-smoker not exposed to second-hand smoke (SHS) as determined by saliva cotinine < 10 ng/ml and tetrahydrocannabinol (THC) < 50 ng/ml.
• Flow mediated dilation of 4% or greater at screening visit.

Exclusion Criteria:

• Age 18 < or > 50 Physician diagnosis of asthma, heart disease, hypertension, thyroid disease, diabetes, renal or liver impairment or glaucoma.

Unstable psychiatric condition (such as current major depression, history of schizophrenia or bipolar disorder) or current use of more than two psychiatric medications Systolic blood pressure > 150 Diastolic blood pressure > 100 Blood glucose > 110 LDL >130 Pregnancy or breastfeeding (by urine Human Chorionic Gonadotropin (hCG) and/or history) Alcohol or illicit drug dependence within the past 5 years BMI > 35 and < 18 Current illicit drug use (by history or urine test) More than 1 pack year smoking history Ever a daily marijuana smoker Smoked anything within the last 3 months Unable to hold allergy or other over-the-counter (OTC) medicines Occupational exposure to smoke, dusts and fumes Concurrent participation in another clinical trial Unable to communicate in English No social security number

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dermal Exposure to Thirdhand Cigarette Smoke; Participants will wear clothing that has been exposed to cigarette smoke, for 3 hours while breathing filtered, temperature and humidity controlled air.	Other: Cigarette Smoke; Cigarette smoke, generated by a smoking machine and aged is used to reproduce exposure to secondhand and thirdhand cigarette smoke.
Active Comparator: Inhalational Exposure to Thirdhand Cigarette Smoke; Participants will breathe cigarette smoke aerosol that has been aged for 22 hours, for 3 hours while wearing clean clothing.	Other: Cigarette Smoke; Cigarette smoke, generated by a smoking machine and aged is used to reproduce exposure to secondhand and thirdhand cigarette smoke.
Active Comparator: Inhalational Exposure to Secondhand Cigarette Smoke; Participants will breathe cigarette smoke aerosol that has been aged for 30 minutes, for 3 hours while wearing clean clothing.	Other: Cigarette Smoke; Cigarette smoke, generated by a smoking machine and aged is used to reproduce exposure to secondhand and thirdhand cigarette smoke.
Sham Comparator: Clean Air Exposure; Participants will breathe filtered, temperature and humidity controlled air while wearing clean clothing for 3 hours.	Other: Clean Air and Clean Clothing/Sham exposure; Clean air, created by high-efficiency particulate air (HEPA) and charcoal filtration and temperature and humidity control. Clean cotton clothing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in flow-mediated dilation (FMD) of the brachial artery, caused by pollution exposures, measured by ultrasound	High-resolution ultrasound of right brachial artery is performed 1 cm distal to antecubital fossa with a 10 megahertz (MHz) linear array probe coupled to a General Electric (GE) Vivid 7 Imaging System. To assess endothelium-dependent dilation, after recording baseline B-mode ultrasound images of the brachial artery and spectral Doppler images of flow velocity, a forearm cuff is inflated to 250 mmHg for 5 minutes to induce reactive hyperemia. Immediately after deflation, Doppler images are obtained to measure reactive hyperemia. FMD of brachial artery will be determined every 15 seconds between 30 and 120 seconds after cuff deflation to capture maximal dilation.The % FMD will be calculated as ratio between the maximum post cuff release brachial artery diameter and baseline diameter. By comparing changes in FMD before exposure, after exposure and next day, we will be able to assess effects of exposure on endothelial function and the potential recovery from these effects.	Baseline (before exposure) 30 minutes (after 30 minutes exposure) and 3 hours.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in trans-epidermal water loss caused by pollution exposures, comparing intact skin to tape-stripped skin	We will measure trans-epidermal water loss (TEWL) on the volar forearm using a dermal relative humidity monitor (model IP52, Delfin Technologies Inc.) on adjacent circles of intact skin and skin that has been tape stripped prior to exposure. By comparing changes in TEWL at these two sites, before and after exposure and at day 2 and day 5, we will be able to detect any effects of dermal cigarette smoke exposure on skin barrier function and the rate of barrier function recovery.	Baseline, 30 minutes, 3 hours, 2 days, 5 days

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: Tobacco Related Disease Research Program
• Investigators: Principal Investigator: Suzaynn F Schick, PhD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2020
• Primary Completion (Estimated): October 31, 2024
• Study Completion (Estimated): October 31, 2024

Study Registration Dates

• First Submitted: June 25, 2019
• First Submitted That Met QC Criteria: July 8, 2019
• First Posted (Actual): July 9, 2019

Study Record Updates

• Last Update Posted (Actual): August 28, 2023
• Last Update Submitted That Met QC Criteria: August 24, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Burns, Inhalation; Burns; Smoke Inhalation Injury
• Other Study ID Numbers: 28PT-0081

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We will share the individual participant data (IPD) that underlie the results in our publications.
• IPD Sharing Time Frame: 9 months after publication
• IPD Sharing Access Criteria: Data will be made available to researchers who submit a detailed and well-supported description of their research plans.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No