Nicotine AddictionPhase 2DUALNCT02870218
Abuse Liability of Reduced Nicotine Content Cigarettes in the Context of Concurrent E-Cigarette Use
A Phase 2 study testing Smoking research cigarettes with e-cigarette and Nicotine discrimination thresholds in people with Nicotine Addiction and Cigarette Smoking, run by Rose Research Center, LLC at 2 sites in United States.
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… Read more about this study
- Who is it for?
- Ages 21 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Nicotine Addiction, Cigarette Smoking
- What is being tested?
- Smoking research cigarettes with e-cigarette and Nicotine discrimination thresholds
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 May 2019to 28 Jul 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
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- e-cigarettes;
- Use in the past 30 days of nicotine replacement therapy or other smoking cessation product
- Positive drug screen for cocaine
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Rose Research Center
Charlotte, North Carolina, 28262
Rose Research Center
Raleigh, North Carolina, 27617
About this study
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.
- Conditions
- Nicotine Addiction, Cigarette Smoking
- Being tested
- Smoking research cigarettes with e-cigarette, Nicotine discrimination thresholds
- Medical subject headings
- Tobacco Use Disorder, Cigarette Smoking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Smoking research cigarettes with e-cigaretteDrug
Also called Spectrum Cigarettes, JUUL e-Cigarette
Smoking research cigarettes with varying levels of nicotine with unlimited access to 15 mg/ml nicotine-containing e-cigarettes.
Nicotine discrimination thresholdsDrug
Also called Halo G6 with Tribeca e-liquid
Measure of nicotine thresholds for detecting and recognizing the addictive, rewarding effects of smoking.
| Study group | Role | What they receive |
|---|---|---|
| 0.40mg Nicotine Cigarette w/ e-Cigarette | Active comparator | Participants will be assigned to smoke 0.40mg nicotine Spectrum cigarettes for 12 weeks with unlimited access to JUUL e-cigarettes.
Smoking research cigarettes with e-cigarette Receives: Drug: Smoking research cigarettes with e-cigarette |
| 1.40mg Nicotine Cigarette w/ e-Cigarette | Active comparator | Participants will be assigned to smoke 1.40mg nicotine Spectrum cigarettes for 12 weeks with unlimited access to JUUL e-cigarettes.
Smoking research cigarettes with e-cigarette Receives: Drug: Smoking research cigarettes with e-cigarette |
| 2.50mg Nicotine Cigarette w/ e-Cigarette | Active comparator | Participants will be assigned to smoke 2.50mg nicotine Spectrum cigarettes for 12 weeks with unlimited access to JUUL e-cigarettes.
Smoking research cigarettes with e-cigarette Receives: Drug: Smoking research cigarettes with e-cigarette |
| 5.60mg Nicotine Cigarette w/ e-Cigarette | Active comparator | Participants will be assigned to smoke 5.60mg nicotine Spectrum cigarettes for 12 weeks with unlimited access to JUUL e-cigarettes.
Smoking research cigarettes with e-cigarette Receives: Drug: Smoking research cigarettes with e-cigarette |
| 16.9mg Nicotine Cigarette w/ e-Cigarette | Active comparator | Participants will be assigned to smoke 16.9mg nicotine Spectrum cigarettes for 12 weeks with unlimited access to JUUL e-cigarettes.
Smoking research cigarettes with e-cigarette Receives: Drug: Smoking research cigarettes with e-cigarette |
| Halo G6 & Tribeca e-liquid | Experimental | Difference detection assessments.
Nicotine discrimination thresholds Receives: Drug: Nicotine discrimination thresholds |
| Spectrum Research Cigarette | Experimental | Difference detection assessments.
Nicotine discrimination thresholds Receives: Drug: Nicotine discrimination thresholds |
What is being measured
The primary outcome is the main question the study is designed to answer.
Expired air CO Measurement
To determine the effects of cigarette nicotine content manipulations on abuse liability as measured by exhaled breath CO.
Measured: 12 Weeks
Secondary outcomes (5)
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.
Measured: Weeks 1, 2,8,10,12 and 14
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.
Measured: Weeks 1, 2,8,10,12 and 14
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.
Measured: 12 Weeks
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.
Measured: 12 Weeks
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.
Measured: 12 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2016 (estimated)
- Study start1 May 2019
- Primary completion28 Jul 2021
- Study completion28 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nicotine AddictionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rose Research Center, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Institutes of Health (NIH), Food and Drug Administration (FDA), National Institute on Drug Abuse (NIDA)
- Responsible party
- Principal investigator, Jed Rose, Rose Research Center, LLC
- Investigators
- Jed E Rose, Ph.D., Principal investigator, Rose Research Center, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02870218
- Sponsor's protocol ID
- 201602820
- Other IDs
- GRANT12052089, 5R01DA042541-03
- Acronym
- DUAL
- Status last verified
- Jan 2022
- First submitted
- 10 Aug 2016
- Last updated
- 14 Jan 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Abuse Liability of Reduced Nicotine Content Cigarettes in the Context of Concurrent E-Cigarette Use
- ClinicalTrials.gov ID
- NCT02870218
- Acronym / sponsor ID
- DUAL / 201602820
- Conditions
- Nicotine Addiction, Cigarette Smoking
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- Rose Research Center, LLCIndustry (pharma, biotech, devices)
- Collaborators
- National Institutes of Health (NIH), Food and Drug Administration (FDA), National Institute on Drug Abuse (NIDA)
- Study start
- 1 May 2019 (actual)
- Primary completion
- 28 Jul 2021 (actual)
- Study completion
- 28 Jul 2021 (actual)
- First posted
- 17 Aug 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| 0.40mg Nicotine Cigarette w/ e-Cigarette | Active comparator | Drug: Smoking research cigarettes with e-cigaretteParticipants will be assigned to smoke 0.40mg nicotine Spectrum cigarettes for 12 weeks with unlimited access to JUUL e-cigarettes. Smoking research cigarettes with e-cigarette |
| 1.40mg Nicotine Cigarette w/ e-Cigarette | Active comparator | Drug: Smoking research cigarettes with e-cigaretteParticipants will be assigned to smoke 1.40mg nicotine Spectrum cigarettes for 12 weeks with unlimited access to JUUL e-cigarettes. Smoking research cigarettes with e-cigarette |
| 2.50mg Nicotine Cigarette w/ e-Cigarette | Active comparator | Drug: Smoking research cigarettes with e-cigaretteParticipants will be assigned to smoke 2.50mg nicotine Spectrum cigarettes for 12 weeks with unlimited access to JUUL e-cigarettes. Smoking research cigarettes with e-cigarette |
| 5.60mg Nicotine Cigarette w/ e-Cigarette | Active comparator | Drug: Smoking research cigarettes with e-cigaretteParticipants will be assigned to smoke 5.60mg nicotine Spectrum cigarettes for 12 weeks with unlimited access to JUUL e-cigarettes. Smoking research cigarettes with e-cigarette |
| 16.9mg Nicotine Cigarette w/ e-Cigarette | Active comparator | Drug: Smoking research cigarettes with e-cigaretteParticipants will be assigned to smoke 16.9mg nicotine Spectrum cigarettes for 12 weeks with unlimited access to JUUL e-cigarettes. Smoking research cigarettes with e-cigarette |
| Halo G6 & Tribeca e-liquid | Experimental | Drug: Nicotine discrimination thresholdsDifference detection assessments. Nicotine discrimination thresholds |
| Spectrum Research Cigarette | Experimental | Drug: Nicotine discrimination thresholdsDifference detection assessments. Nicotine discrimination thresholds |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (9 listed)
- 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:
- Use in the past 30 days of nicotine replacement therapy or other smoking cessation product
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Smoking research cigarettes with e-cigaretteAlso: Spectrum Cigarettes, JUUL e-CigaretteSmoking research cigarettes with varying levels of nicotine with unlimited access to 15 mg/ml nicotine-containing e-cigarettes. | Drug | 0.40mg Nicotine Cigarette w/ e-Cigarette, 1.40mg Nicotine Cigarette w/ e-Cigarette, 16.9mg Nicotine Cigarette w/ e-Cigarette, 2.50mg Nicotine Cigarette w/ e-Cigarette, 5.60mg Nicotine Cigarette w/ e-Cigarette |
| Nicotine discrimination thresholdsAlso: Halo G6 with Tribeca e-liquidMeasure of nicotine thresholds for detecting and recognizing the addictive, rewarding effects of smoking. | Drug | Halo G6 & Tribeca e-liquid, Spectrum Research Cigarette |
Primary outcome
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.
5 secondary outcomes
Nicotine discrimination tests to determine nicotine detection thresholds
Time frame: Weeks 1, 2,8,10,12 and 14
Nicotine discrimination tests to determine nicotine recognition thresholds
Time frame: Weeks 1, 2,8,10,12 and 14
Extent of e-cigarette use based on self-report
Time frame: 12 Weeks
Extent of e-cigarette use based on self-report cotinine levels
Time frame: 12 Weeks
Mean number of research cigarettes smoked per day as primary index of abuse liability
Time frame: 12 Weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jed E Rose, Ph.D. principal investigator
Rose Research Center, LLC
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Smoking research cigarettes with e-cigarette and Nicotine discrimination thresholds in people with Nicotine Addiction and Cigarette Smoking, run by Rose Research Center, LLC at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Expired air CO Measurement (time frame: 12 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2022.