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

Cigarette Smoking Clinical Trial

— DUAL  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02870218
• Other study ID #: 201602820
• Secondary ID: GRANT120520895R0
• Status: Completed
• Phase: Phase 2
• Start date: May 1, 2019
• Est. completion date: July 28, 2021

Study information

• Verified date: January 2022
• Source: Rose Research Center, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: July 28, 2021
• Est. primary completion date: July 28, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Cigarette Smoking
• Nicotine Addiction
• Tobacco Use Disorder

Intervention

Drug:
• Smoking research cigarettes with e-cigarette
Smoking research cigarettes with varying levels of nicotine with unlimited access to 15 mg/ml nicotine-containing e-cigarettes.
• Nicotine discrimination thresholds
Measure of nicotine thresholds for detecting and recognizing the addictive, rewarding effects of smoking.

Locations

Country	Name	City	State
United States	Rose Research Center	Charlotte	North Carolina
United States	Rose Research Center	Raleigh	North Carolina

Sponsors (4)

Lead Sponsor	Collaborator
Rose Research Center, LLC	Food and Drug Administration (FDA), National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Expired air CO Measurement	To determine the effects of cigarette nicotine content manipulations on abuse liability as measured by exhaled breath CO.	12 Weeks
Secondary	Nicotine discrimination tests to determine nicotine detection thresholds	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.	Weeks 1, 2,8,10,12 and 14
Secondary	Nicotine discrimination tests to determine nicotine recognition thresholds	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.	Weeks 1, 2,8,10,12 and 14
Secondary	Extent of e-cigarette use based on self-report	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.	12 Weeks
Secondary	Extent of e-cigarette use based on self-report cotinine levels	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.	12 Weeks
Secondary	Mean number of research cigarettes smoked per day as primary index of abuse liability	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.	12 Weeks