Randomized Controlled Trial Methods for Novel Tobacco Products Evaluation

The purpose of this study is to use Randomized Controlled Trial (RCT) methods to examine the influence of novel tobacco products on biomarkers of toxicant exposure and disease risk, reports of adverse events, and concurrent use of other tobacco products. In this case, the novel products are one type of electronic cigarette and an imitation cigarette or cigarette substitute.

Study Overview

• Status: Completed
• Conditions: Nontherapeutic
• Intervention / Treatment: Other: cigarette substitute; Other: e-cigarette

• Study Type: Interventional
• Enrollment (Actual): 520
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S. Hershey Medical Center
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Center for the Study of Tobacco Products

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 21-65
• Smoke >9 cigarettes per day for at least 1 year
• Smoke regular filtered cigarettes or machine-rolled cigarettes with a filter
• CO measurement >9 ppm at baseline
• No serious quit attempt in the prior 1 month. This includes use of any FDA approved smoking cessation medication (varenicline, bupropion [used specifically as a quitting aid], patch, gum, lozenge, inhaler, and nasal spray) in the past 1 month as an indication of treatment seeking.
• Not planning to quit in the next 6 months
• Interested in reducing cigarette consumption
• Willing to attend visits weekly and monthly over a 9-month period (not planning to move, not planning extended vacation, no planned surgeries)
• Read and write in English
• Able to understand and consent

Exclusion Criteria:

• Pregnant and/or nursing women
• Unstable or significant medical condition in the past 12 months (Recent heart attack or some other heart conditions, stroke, severe angina including high blood pressure if systolic >159 or diastolic >99 observed during screening).
• Immune system disorders, respiratory diseases (exacerbations of asthma or COPD, require oxygen, require oral prednisone), kidney (dialysis) or liver diseases (cirrhosis), or any medical disorder/medication that may affect participant safety or biomarker data.
• Use of any non-cigarette nicotine delivery product (pipe, cigar, dip, chew, snus, hookah, ECIGs, strips, sticks) in the past 7 days
• Uncontrolled mental illness or substance abuse or inpatient treatment for these in the past 6 months
• History of difficulty providing or unwilling to provide blood samples (fainting, poor veins, anxiety)
• No surgery requiring general anesthesia in the past 6 weeks
• Use of an ECIG for 5 or more days in the past 28 days or any use in the past 7 days
• Use of marijuana or any illicit drug/prescription drugs for non-medical use daily/almost daily, or weekly in the past 3 months per NIDA Quick Screen
• Use of hand-rolled, roll your own cigarettes
• Known allergy to propylene glycol or vegetable glycerin
• Other member of household is currently participating/participated in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: cigarette substitute; The QuitSmart cigarette substitute is a plastic tube that looks like a real cigarette and is designed to provide the same draw resistance as a smoker's usual cigarette. There is no drug delivery with this product. Two cigarette substitutes and a product manual are provided to participants following randomization and replacement products are provided throughout the intervention period (24 weeks).	Other: cigarette substitute
Experimental: e-cigarette (with 0 mg/ml nicotine); The e-cigarette used will be the EGO e-cigarette (marketed by www.liquidexpress.com). Each participant randomized to an ECIG condition will receive 2 e-cigarette batteries, 1 wall adapter, 1 USB charger, and a user manual. Cartomizers containing 0 mg/ml nicotine will be provided throughout the intervention period (24 weeks).	Other: e-cigarette
Experimental: e-cigarette (with 8 mg/ml nicotine); The e-cigarette used will be the EGO e-cigarette (marketed by www.liquidexpress.com). Each participant randomized to an ECIG condition will receive 2 e-cigarette batteries, 1 wall adapter, 1 USB charger, and a user manual. Cartomizers containing 8 mg/ml nicotine will be provided throughout the intervention period (24 weeks).	Other: e-cigarette
Experimental: e-cigarette (with 36 mg/ml nicotine); The e-cigarette used will be the EGO e-cigarette (marketed by www.liquidexpress.com). Each participant randomized to an ECIG condition will receive 2 e-cigarette batteries, 1 wall adapter, 1 USB charger, and a user manual. Cartomizers containing 36 mg/ml nicotine will be provided throughout the intervention period (24 weeks).	Other: e-cigarette

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
urine carcinogen biomarker of exposure, NNAL	changes in NNAL concentration measured at week 0, week 4, week 12, and week 24	week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
urine biomarker of nicotine exposure, cotinine	changes in cotinine concentration measured at week 0, week 4, week 12, and week 24	week 24
blood, urine, and exhaled breath condensate biomarkers of oxidative stress, glutathione and 8 Isoprostanes	changes in oxidative stress biomarker concentrations measured at week 0, week 4, week 12, and week 24	week 24

Collaborators and Investigators

• Sponsor: Virginia Commonwealth University
• Collaborators: National Institute on Drug Abuse (NIDA); Penn State University; Food and Drug Administration (FDA)
• Investigators: Principal Investigator: Thomas Eissenberg, Virginia Commonwealth University

Publications and helpful links

General Publications

• Cobb CO, Foulds J, Yen MS, Veldheer S, Lopez AA, Yingst JM, Bullen C, Kang L, Eissenberg T; Randomised Control Trial Methods Workgroup of the Center for the Study of Tobacco Products. Effect of an electronic nicotine delivery system with 0, 8, or 36 mg/mL liquid nicotine versus a cigarette substitute on tobacco-related toxicant exposure: a four-arm, parallel-group, randomised, controlled trial. Lancet Respir Med. 2021 Aug;9(8):840-850. doi: 10.1016/S2213-2600(21)00022-9. Epub 2021 Apr 12.
• Lopez AA, Cobb CO, Yingst JM, Veldheer S, Hrabovsky S, Yen MS, Foulds J, Eissenberg T. A transdisciplinary model to inform randomized clinical trial methods for electronic cigarette evaluation. BMC Public Health. 2016 Mar 3;16:217. doi: 10.1186/s12889-016-2792-8.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2015
• Primary Completion (Actual): June 1, 2018
• Study Completion (Actual): July 1, 2018

Study Registration Dates

• First Submitted: December 16, 2014
• First Submitted That Met QC Criteria: January 15, 2015
• First Posted (Estimate): January 21, 2015

Study Record Updates

• Last Update Posted (Actual): September 7, 2018
• Last Update Submitted That Met QC Criteria: September 6, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: HM20002759; 5P50DA036105-02 (U.S. NIH Grant/Contract)