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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04003805
Recruitment Status : Not yet recruiting
First Posted : July 1, 2019
Last Update Posted : August 27, 2020
Sponsor:
Collaborator:
National Institute on Drug Abuse (NIDA)
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Brief 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.

Condition or disease Intervention/treatment Phase
Smoking, Cigarette Drug: Standardized Research E-cigarette (SREC) Drug: Nicotine Mini-Lozenge Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 125 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Biomarkers of Exposure and Effect in Standardized Research E-cigarette (SREC) Users
Estimated Study Start Date : November 2020
Estimated Primary Completion Date : September 15, 2021
Estimated Study Completion Date : January 15, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: E-Cigarettes

Arm Intervention/treatment
Experimental: Switching from Smoking Cigarettes to SREC 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

Experimental: Switching from Smoking Cigarettes to Nicotine Mini-Lozenge Drug: 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).

No Intervention: Usual Brand Cigarettes



Primary Outcome Measures :
  1. Exposure Biomarkers [ Time Frame: 1 Year ]
    Difference in TNE (biomarker of nicotine) between patients using medicinal nicotine products and usual brand cigarettes.

  2. Exposure Biomarkers [ Time Frame: 1 Year ]
    Difference in total NNAL between patients using medicinal nicotine products and usual brand cigarettes.

  3. Exposure Biomarkers [ Time Frame: 1 Year ]
    Difference in total NNN (TSNA biomarkers) between patients using medicinal nicotine products and usual brand cigarettes.

  4. Exposure Biomarkers [ Time Frame: 1 Year ]
    Difference in PheT (PAH biomarker) between patients using medicinal nicotine products and usual brand cigarettes.

  5. Exposure Biomarkers [ Time Frame: 1 Year ]
    Difference in mercapturic acids HMPMA between patients using medicinal nicotine products and usual brand cigarettes.

  6. Exposure Biomarkers [ Time Frame: 1 Year ]
    Difference in 2-HPMA between patients using medicinal nicotine products and usual brand cigarettes.

  7. Exposure Biomarkers [ Time Frame: 1 Year ]
    Difference in 3-HPMA (biomarkers of VOC) between patients using medicinal nicotine products and usual brand cigarettes.

  8. Formaldehyde-DNA adducts [ Time Frame: 8 Weeks ]
    Changes in inflammatory biomarkers at 4 and 8 weeks after randomization.

  9. Oxidative DNA adduct 8-oxo-dG in DNA [ Time Frame: 8 Weeks ]
    Changes in DNA adducts at 4 and 8 weeks after randomization.

  10. Salivary NNN [ Time Frame: 1 Year ]
    Levels of NNN and nornicotine in saliva in oral cells of complete switchers to SREC and medicinal nicotine.

  11. NNN-derived HPB-releasing DNA adducts [ Time Frame: 1 Year ]
    Levels of HPB-releasing DNA adducts in oral cells of complete switchers to SREC and medicinal nicotine.


Secondary Outcome Measures :
  1. Product Use [ Time Frame: 1 Year ]
    For cigarettes, cigarettes per day will be assessed based on Interactive Voice Response (IVR) system.

  2. Product Use [ Time Frame: 1 Year ]
    For SREC, number of bouts will be assessed based on IVR system

  3. Product Use [ Time Frame: 1 Year ]
    For SREC, estimated number of puffs will be assessed based on IVR system.

  4. Product Use [ Time Frame: 1 Year ]
    For SREC, amount of e-liquid consumed will be assessed by difference in cartridge weights before and after use.

  5. Product Use [ Time Frame: 1 Year ]
    For medicinal nicotine, daily number of mini-lozenges will be assessed based on based on IVR system and counting returned unused product.

  6. Cigarette Avoidance [ Time Frame: 1 Year ]
    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).

  7. Cigarette Avoidance [ Time Frame: 1 Year ]
    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).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04003805


Contacts
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Contact: Hanna Vanderloo, RN, MSN 612.624.4983 hannav@umn.edu

Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
National Institute on Drug Abuse (NIDA)
Investigators
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Principal Investigator: Irina Stepanov, PhD University of Minnesota, Division of Environmental Health Sciences
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Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT04003805    
Other Study ID Numbers: 2018NTLS016/SPH-2018-25712
First Posted: July 1, 2019    Key Record Dates
Last Update Posted: August 27, 2020
Last Verified: August 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Nicotine
Ganglionic Stimulants
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action