Clinical trial NCT02870218: Abuse Liability of Reduced Nicotine Content Cigarettes in the Context of Concurrent E-Cigarette Use
Official title: Abuse Liability of Reduced Nicotine Content Cigarettes in the Context of Concurrent E-Cigarette Use
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Nicotine Addiction
Cigarette Smoking
Lead sponsor: Rose Research Center, LLC
Sponsor class: INDUSTRY
Collaborators: name: National Institutes of Health (NIH)
name: Food and Drug Administration (FDA)
name: National Institute on Drug Abuse (NIDA)
First posted: 2016-08-17
Enrollment: 150
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. 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).
2. Subject smokes on average four days a week for the last 12 months.
3. Subject has no intention of quitting smoking within the next 90 days.
4. Owns a smart phone with text message and data capabilities.
5. Willingness to use and ability to operate e-cigarettes.
6. Willingness to smoke Research Cigarettes.

Exclusion Criteria:

1. 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.
2. Severe or uncontrolled psychiatric disease with the exception of anxiety disorders, obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD);
3. Pregnant or nursing (by self-report) or positive pregnancy test;
4. Daily use of:

   1. Experimental (investigational) drugs that are unknown to subject;
   2. Smokeless tobacco (chewing tobacco, snuff), cigars, pipes and hookah;
   3. e-cigarettes;
5. Use in the past 30 days of nicotine replacement therapy or other smoking cessation product
6. Positive drug screen for cocaine

Primary outcomes:
measure: Expired air CO Measurement
timeFrame: 12 Weeks
Secondary outcomes:
measure: Nicotine discrimination tests to determine nicotine detection thresholds
timeFrame: Weeks 1, 2,8,10,12 and 14
measure: Nicotine discrimination tests to determine nicotine recognition thresholds
timeFrame: Weeks 1, 2,8,10,12 and 14
measure: Extent of e-cigarette use based on self-report
timeFrame: 12 Weeks
measure: Extent of e-cigarette use based on self-report cotinine levels
timeFrame: 12 Weeks
measure: Mean number of research cigarettes smoked per day as primary index of abuse liability
timeFrame: 12 Weeks
Other outcomes:
Locations:
city: Charlotte
country: United States
facility: Rose Research Center
state: North Carolina
city: Raleigh
country: United States
facility: Rose Research Center
state: North Carolina
Study officials:
affiliation: Rose Research Center, LLC
name: Jed E Rose, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: