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Completed

NCT Number: NCT02870218

Abuse Liability of Reduced Nicotine Content Cigarettes in the Context of Concurrent E-Cigarette Use

Three hundred-twenty (320) adult smokers of menthol or non-menthol combustible cigarettes will be recruited and randomly assigned to one of five groups (n=64/group), who will be asked to switch for 12 weeks to ad libitum use of combustible cigarettes (matched to subjects' menthol preference) containing either 0.4, 1.4, 2.5, 5.6 or 16.9 mg nicotine (standardized nicotine yields ranging from 0.02-0.80 mg/cigarette), respectively. Each group will include 32 heavy (≥ 20 cigarettes/day), and 32 light smokers (≤10 cigarettes/day), who are hypothesized to be more sensitive to nicotine's reinforcing effects. Participants will also have free access to nicotine-containing e-cigarettes (JUUL) throughout the 12-week period. Abuse liability of combustible cigarettes will be assessed by behavioral (cigarettes/day, time to first cigarettes), self-report (rewarding effects, withdrawal symptoms) and biochemical indices (expired air carbon monoxide, cotinine blood sampling).

In laboratory sessions, we will measure nicotine thresholds for detecting and recognizing the addictive, rewarding effects of smoking. This study is designed to help the FDA identify a target nicotine threshold that will not attract young people to smoking or induce relapse in former smokers. Additionally, we will determine the level of cigarette nicotine reduction that will be tolerated without inducing dissatisfaction in smokers, information that is relevant to the FDA for designing a stepwise nicotine reduction policy that can be implemented without widespread objections. The knowledge gained from this project will greatly increase our knowledge of nicotine addiction and will help frame an FDA policy relating to the regulation of the nicotine content of tobacco. Ultimately, a well-designed nicotine reduction policy has the potential to greatly reduce the enormous toll of death and disease caused by cigarette smoking.

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Key information

Conditions

Nicotine Addiction Behavior Chemically-Induced Disorders Cigarette Smoking Mental Disorders Smoking Substance-Related Disorders Tobacco Smoking Tobacco Use Tobacco Use Disorder

Age range

21 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Rose Research Center, Charlotte, North Carolina, United States

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Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Subject is healthy as judged by the Investigator based on all available assessments from the Screening Period (e.g., safety laboratory, vital signs, physical examination, ECG, concomitant medications and medical history).
  • Subject smokes on average four days a week for the last 12 months.
  • Subject has no intention of quitting smoking within the next 90 days.
  • Owns a smart phone with text message and data capabilities.
  • Willingness to use and ability to operate e-cigarettes.
  • Willingness to smoke Research Cigarettes.

Exclusion criteria

  • Any medical or psychiatric condition (or associated symptoms or medications) determined by a medical professional to be severe enough to be disruptive to the study.
  • Severe or uncontrolled psychiatric disease with the exception of anxiety disorders, obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD);
  • Pregnant or nursing (by self-report) or positive pregnancy test;
  • Daily use of:
  • Experimental (investigational) drugs that are unknown to subject;
  • Smokeless tobacco (chewing tobacco, snuff), cigars, pipes and hookah;
  • e-cigarettes;
  • Use in the past 30 days of nicotine replacement therapy or other smoking cessation product
  • Positive drug screen for cocaine

Treatment and study plan

Smoking research cigarettes with e-cigarette

Drug

Smoking research cigarettes with varying levels of nicotine with unlimited access to 15 mg/ml nicotine-containing e-cigarettes.

Other names: Spectrum Cigarettes, JUUL e-Cigarette

Nicotine discrimination thresholds

Drug

Measure of nicotine thresholds for detecting and recognizing the addictive, rewarding effects of smoking.

Other names: Halo G6 with Tribeca e-liquid

Primary outcomes

  1. Expired air CO Measurement

    Time frame: 12 Weeks

    To determine the effects of cigarette nicotine content manipulations on abuse liability as measured by exhaled breath CO.

Secondary outcomes

  1. Nicotine discrimination tests to determine nicotine detection thresholds

    Time frame: Weeks 1, 2,8,10,12 and 14

    Results of the laboratory discrimination tests will be analyzed descriptively to determine nicotine detection thresholds. Thresholds will be calculated based on both group-averaged data as well as by using the best estimates of individual thresholds calculated from each smoker's data. Group averaged data will be determined by graphically plotting the overall percent correct against nicotine concentration.

  2. Nicotine discrimination tests to determine nicotine recognition thresholds

    Time frame: Weeks 1, 2,8,10,12 and 14

    Results of the laboratory discrimination tests will be analyzed descriptively to determine nicotine recognition thresholds. Thresholds will be calculated based on both group-averaged data as well as by using the best estimates of individual thresholds calculated from each smoker's data. Group averaged data will be determined by graphically plotting the overall percent correct against nicotine concentration.

  3. Extent of e-cigarette use based on self-report

    Time frame: 12 Weeks

    To determine whether the abuse liability of combustible cigarettes is related to the nicotine intake from e-cigarettes or to total nicotine intake, regression analyses will be conducted to correlate indices of abuse liability to levels of cotinine as well as to the estimated intake of nicotine from cigarettes and e-cigarettes based on self-reported values.

  4. Extent of e-cigarette use based on self-report cotinine levels

    Time frame: 12 Weeks

    To determine whether the abuse liability of combustible cigarettes is related to the nicotine intake from e-cigarettes or to total nicotine intake, regression analyses will be conducted to correlate indices of abuse liability to levels of cotinine as well as to the estimated intake of nicotine from cigarettes and e-cigarettes.

  5. Mean number of research cigarettes smoked per day as primary index of abuse liability

    Time frame: 12 Weeks

    To assess the effects of cigarette nicotine content on abuse liability among smokers who also use e-cigarettes. The primary index of abuse liability will be mean number of research cigarettes smoked per day. Secondary outcome measures comprise expired air carbon monoxide (CO), Fagerström Test for Nicotine Dependence (FTND) score, withdrawal symptoms and cognitive performance.

Sponsors and collaborators

Lead sponsor

Rose Research Center, LLC

Industry

Collaborators

  • Food and Drug Administration (FDA)
  • National Institute on Drug Abuse (NIDA)
  • National Institutes of Health (NIH)

Registry information

Acronym: DUAL

Important dates

Study start
2019
Primary completion
2021
Study completion
2021
First posted
Aug 17, 2016
Registry last updated
Jan 14, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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