Biomarkers of Exposure and Effect in Standardized Research E-cigarette (SREC) Users

Smoking, Cigarette Clinical Trial

Official title:

Biomarkers of Exposure and Effect in Standardized Research E-cigarette (SREC) Users

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04003805
• Other study ID #: 2018NTLS016
• Status: Recruiting
• Phase: Phase 1
• Start date: May 11, 2022
• Est. completion date: January 20, 2025

Study information

• Verified date: February 2024
• Source: Masonic Cancer Center, University of Minnesota
• Contact: Hanna Vanderloo, RN, MSN
• Phone: 612.624.4983
• Email: hannav[@]umn.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is focused on characterizing the toxic and carcinogenic potential of the Standardized Research E-cigarette (SREC) developed by the National Institute on Drug Abuse. In the environment of continuously changing e-cigarette market, SREC was developed as a model e-cigarette that will remain available for an extended period of time and can be used as a bridging element in various studies aimed at evaluating the value and limitations of e-cigarettes as tobacco risk reduction tools. Our overall goal is to generate initial reference data on chemical exposures and associated effects in smokers switching to SREC.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 125
• Est. completion date: January 20, 2025
• Est. primary completion date: July 19, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Male or female smokers who are 18-65 years of age and are willing to stop smoking and completely switch to e-cigarettes or medicinal nicotine;
• Report smoking = 5 cigarettes daily and not using any other nicotine or tobacco product;
• Biochemically confirmed regular smoking status by a NicAlert test level of 6;
• Smoking daily for at least 1 year and no serious quit attempts (e.g., quit for 24 hours or longer) in the last 3 months (to ensure stability of daily smoking, particularly for those randomized to the continued smoking group);
• No unstable and significant medical or psychiatric conditions as determined by medical history and Prime-MD (to ensure safety of the subject, to minimize the effects of poor health on biomarker measures and to maximize compliance to study procedures);
• Subjects are in good physical health (no unstable medical condition);
• Subjects are in stable, good mental health (e.g. not currently, within the past 6 months, experiencing unstable or untreated psychiatric diagnosis, including substance abuse);
• Subjects who are not taking anti-inflammatory medications or any medications that affect relevant metabolic enzymes;
• Women who are not pregnant or nursing or planning to become pregnant;
• Subject has provided written informed consent to participate in the study (adolescents under the age of 18 will be excluded because this project involves continued use of tobacco products and new tobacco products).

Exclusion Criteria:

• Regular tobacco or nicotine product use (e.g., 9 days in last 30 days) other than cigarettes;
• Currently using nicotine replacement or other tobacco cessation products;
• Significant immune system disorders, respiratory diseases, kidney or liver diseases or any other medical disorders that may affect biomarker data;
• Unstable health conditions (any significant serious, unstable medical condition including, but not limited to, cardiovascular disease, unstable COPD, seizure disorder and cancer, as determined by the licensed medical professional);
• Unstable mental health (to be determined by medical history, CESD, Prime-MD after review by the licensed medical professional);
• Excessive drinking (e.g., 5 or more drinks daily) or problems with drinking or drugs (e.g., self-report of binge drinking alcohol or treatment for drug or alcohol abuse within last 3 months); to be assessed by PI or licensed medical professional;
• Blood alcohol test > 0.01 (g/dL) as measured by a breath sample at screening (participants failing the breath alcohol screen will be allowed to re-screen once;
• Positive toxicology screen for any of the following drugs: cocaine, opiates, methadone, benzodiazepines, barbiturates, amphetamines, methamphetamines, and PCP. Failing temperature strip for the sample. Marijuana will be tested for, but will not be an exclusionary criterion. Participants with valid prescriptions for opiates, benzodiazepines, barbiturates, amphetamines or methadone will not be excluded. Participants failing the toxicology screen will be allowed to re-screen once;
• Pregnant or breastfeeding;
• Failure to agree to take adequate protection to avoid becoming pregnant during the study;
• Vital signs outside of the following range (participants failing for vital signs will

be allowed to re-screen once):

• Systolic BP greater than or equal to 160 mm/hg
• Diastolic BP greater than or equal to 100 mm/hg
• Systolic BP below 90 mm/hg and symptomatic (dizziness, extreme fatigue, difficulty thinking, inability to stand or walk, feeling faint)
• Diastolic BP below 50 mm/hg and symptomatic (dizziness, extreme fatigue, difficulty thinking, inability to stand or walk, feeling faint)
• Heart rate greater than or equal to 105 bpm
• Heart rate lower than 45 bpm and symptomatic (dizziness, extreme fatigue, difficulty thinking, inability to stand or walk, feeling faint)
• Expired air carbon monoxide (CO) level greater than 80 ppm;
• Self-reported allergies to propylene glycol or vegetable glycerin;
• Adverse reactions when previously using electronic cigarettes;
• Household member enrolled in the study concurrently;
• Unable to read for comprehension or completion of study documents;
• Unstable living environment that would compromise the ability to attend visits, sequester study products or complete study procedures outside of visits.

Related Conditions & MeSH terms

• Smoking, Cigarette

Intervention

Drug:
• Standardized Research E-cigarette (SREC)
The device operates at a single output voltage (3.30 ± 0.05 V) and uses sealed disposable 3-mL cartridges with tobacco-flavored e-liquid (~350 puffs/cartridge). The concentration of nicotine in e-liquid is 15 mg/mL, and the vehicle composition is 50:50 propylene glycol and glycerin. The device uses a battery that can be recharged via a micro USB port. A single charge is designed to sustain more than 400 puffs, which is more than the capacity of an e-liquid cartridge. The e-liquid and the aerosol are well-characterized in terms of chemical impurities and by-products (such as aldehydes), which are minimal. Additional information, including the results of pharmacokinetics study is available via NIDA website: https://www.drugabuse.gov/funding/supplemental-information-nida-e-cig
• Nicotine Mini-Lozenge
We will use commercially available nicotine mini-lozenges containing 2 or 4 mg nicotine/lozenge (Nicorette, manufactured by GlaxoSmithKline). Dose will be determined per instructions on the package (e.g, if smoking within 30 minutes upon awakening, then 4 mg dose will be prescribed).

Locations

Country	Name	City	State
United States	University of Minnesota, Masonic Cancer Center	Minneapolis	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Masonic Cancer Center, University of Minnesota	National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Exposure Biomarkers	Difference in TNE (biomarker of nicotine) between patients using medicinal nicotine products and usual brand cigarettes.	1 Year
Primary	Exposure Biomarkers	Difference in total NNAL between patients using medicinal nicotine products and usual brand cigarettes.	1 Year
Primary	Exposure Biomarkers	Difference in total NNN (TSNA biomarkers) between patients using medicinal nicotine products and usual brand cigarettes.	1 Year
Primary	Exposure Biomarkers	Difference in PheT (PAH biomarker) between patients using medicinal nicotine products and usual brand cigarettes.	1 Year
Primary	Exposure Biomarkers	Difference in mercapturic acids HMPMA between patients using medicinal nicotine products and usual brand cigarettes.	1 Year
Primary	Exposure Biomarkers	Difference in 2-HPMA between patients using medicinal nicotine products and usual brand cigarettes.	1 Year
Primary	Exposure Biomarkers	Difference in 3-HPMA (biomarkers of VOC) between patients using medicinal nicotine products and usual brand cigarettes.	1 Year
Primary	Formaldehyde-DNA adducts	Changes in inflammatory biomarkers at 4 and 8 weeks after randomization.	8 Weeks
Primary	Oxidative DNA adduct 8-oxo-dG in DNA	Changes in DNA adducts at 4 and 8 weeks after randomization.	8 Weeks
Primary	Salivary NNN	Levels of NNN and nornicotine in saliva in oral cells of complete switchers to SREC and medicinal nicotine.	1 Year
Primary	NNN-derived HPB-releasing DNA adducts	Levels of HPB-releasing DNA adducts in oral cells of complete switchers to SREC and medicinal nicotine.	1 Year
Secondary	Product Use	For cigarettes, cigarettes per day will be assessed based on Interactive Voice Response (IVR) system.	1 Year
Secondary	Product Use	For SREC, number of bouts will be assessed based on IVR system	1 Year
Secondary	Product Use	For SREC, estimated number of puffs will be assessed based on IVR system.	1 Year
Secondary	Product Use	For SREC, amount of e-liquid consumed will be assessed by difference in cartridge weights before and after use.	1 Year
Secondary	Product Use	For medicinal nicotine, daily number of mini-lozenges will be assessed based on based on IVR system and counting returned unused product.	1 Year
Secondary	Cigarette Avoidance	SREC or Medicinal Nicotine: the number of cigarette avoidance days, defined as no tobacco cigarettes smoked in the past 24 hours based on IVR, and the rate of cigarette avoidance, calculated as the proportion of cigarette avoidance days out of the total number of days in the product use period (56 days for those who complete the study).	1 Year
Secondary	Cigarette Avoidance	SREC or Medicinal Nicotine: rate of cigarette avoidance, calculated as the proportion of cigarette avoidance days out of the total number of days in the product use period (56 days for those who complete the study).	1 Year