Tobacco DependencePhase 2NCT00777569
Comparisons of Nicotine-free Cigarettes, Extra Low Nicotine Cigarettes vs. Medicinal Nicotine
A Phase 2 study testing Nicotine free cigarettes, Extra-low nicotine cigarettes and Nicotine Lozenge in people with Tobacco Dependence, run by National Institute on Drug Abuse (NIDA) at 1 site in United States.
Trial summary
In this study, smokers will be randomly assigned to one of three conditions for six weeks: 1) nicotine-free cigarettes (0.05mg); 2) extra low nicotine cigarettes (0.3 mg); or 3) medicinal 4 mg nicotine lozenge. The tobacco toxin profiles across these various products will be compared. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Tobacco Dependence
- What is being tested?
- Nicotine free cigarettes, Extra-low nicotine cigarettes and Nicotine Lozenge
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2005to Nov 2006
- 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 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- smoking between 10-40 cigarettes daily for the past year;
- in good physical health (no unstable medical condition;
- no contraindications for medicinal nicotine;
- stable, good mental health
Who cannot join
- unwilling to use study products for 6 weeks;
- unstable medical or psychiatric condition.
Trial locations and contacts
1 site in 1 country.
United States1 site
Univerisity of Minnesota
Minneapolis, Minnesota, 55414
About this study
Official title: Study 2: Comparisons of Nicotine-free Cigarettes, Extra Low Nicotine Cigarettes vs. Medicinal Nicotine
In this study, smokers will be randomly assigned to one of three conditions for six weeks: 1) nicotine-free cigarettes (0.05mg); 2) extra low nicotine cigarettes (0.3 mg); or 3) medicinal 4 mg nicotine lozenge. The tobacco toxin profiles across these various products will be compared. The effects of these products on biomarkers of exposure and risk factors for disease, compensatory smoking, components of tobacco addiction and short-term smoking cessation will be determined. Predictors of response to these products (e.g., compensatory smoking, compliance with product use, time to lapse) will also be examined.
The following primary hypothesis will be tested: 1) Extent of tobacco toxin exposure will be greatest for the extra low nicotine cigarette and least for nicotine lozenge. Other secondary hypotheses include: 2) Compensatory smoking, as calculated by using cotinine, will be greatest for the extra low cigarette compared to the nicotine-free cigarette; 3) Greater positive subjective responses to cigarettes will be observed with extra low nicotine vs. nicotine-free cigarette; 4) Similar withdrawal symptoms and negative affect will be observed with nicotine-free cigarette and nicotine lozenge, and least withdrawal and negative affect with the extra low nicotine cigarette; 6) Least dependence and greatest motivation and self-efficacy to quit will be observed with nicotine lozenge and the greatest dependence and least motivation and self-efficacy to quit with the extra low nicotine cigarette use; 7) Shorter time to lapse will be observed with extra low nicotine vs. nicotine-free cigarettes because of extinction is likely to occur with nicotine-free cigarettes, and the longest time to lapse for nicotine lozenge because the cigarette condition groups will have experienced stronger attentional bias toward cues, and more dependence prior to the quit date and greater withdrawal after the quit date.
Read the detailed description
Smokers (N=150) will be enrolled in the study and will smoke ad libitum for a period of two weeks during which time they will be assessed for baseline measurements. Subjects will then be randomly assigned to one of the three conditions (N=50). Subjects will be blinded as to whether they are assigned to the Quest nicotine-free vs. extra low nicotine condition. There are no distinguishing features between these two cigarettes. Nicotine lozenge assignment is open label. Subjects will be asked to use only their assigned study product (low nicotine, nicotine-free cigarettes or lozenge) for a period of 6 weeks. Study cigarettes will be given to them at each clinic visit and subjects will be told to smoke ad libitum. They will be provided a supply equivalent to 150% of their baseline-smoking rate to allow for compensatory smoking to occur. They will keep record of each cigarette they smoked. If they smoked cigarettes other than those assigned to them, they will be asked to notate on a sheet when that cigarette was smoked. At the end of the 6-week period, they will be asked to quit smoking and NRT.
First morning urine and fasting blood samples will be collected at baseline and 2 and 6 weeks on the study products; at 6 weeks of abstinence and the 1 month follow-up.
Counseling. In each condition, subjects will be provided brief, structured counseling that is similar in duration. The subjects in the cigarette conditions will discuss any difficulties they experienced with switching cigarettes and problem solving these obstacles. Problem solving each obstacle will be solicited from the subject. However, if no solution or limited solution is provided, the counselor will provide a standardized response for each of the obstacles confronted.
Follow-up Phase. Subjects will be followed up 1 month after the end of the 6 week abstinence period.
- Conditions
- Tobacco Dependence
- Being tested
- Nicotine free cigarettes, Extra-low nicotine cigarettes, Nicotine Lozenge
- Keywords
- Smoking, PREPS, Harm reduction, Biomarkers of tobacco exposure, Compensatory smoking
- Medical subject headings
- Tobacco Use Disorder, Smoking, Harm Reduction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nicotine free cigarettesDrug
Quest Step 2 contains 0.05 mg nicotine
Extra-low nicotine cigarettesDrug
Quest 2 cigarettes contains 0.3 mg nicotine
Nicotine LozengeDrug
Also called Commit
4 mg nicotine lozenge
| Study group | Role | What they receive |
|---|---|---|
| Extra-low nicotine cigarettes | Experimental | Not described Receives: Drug: Extra-low nicotine cigarettes |
| Nicotine-free cigarettes | Experimental | Not described Receives: Drug: Nicotine free cigarettes |
| Medicinal Nicotine | Active comparator | Not described Receives: Drug: Nicotine Lozenge |
What is being measured
The primary outcome is the main question the study is designed to answer.
Biomarkers for tobacco exposure measures: Carbon monoxide, cotinine, NNAL-gluc, NNN, mercapturic acids, 1-hydroxypytrene and biomarkers for cardiovascular risk: WBC, lipid profile, fibrinogen, heart rate, blood pressure.
Measured: 6 weeks
Tobacco Cessation
Measured: 12 weeks
Secondary outcomes (5)
Pulmonary function
Measured: 12 weeks
Nicotine withdrawal symptoms
Measured: 12 weeks
Motivation to quit and self-efficacy
Measured: 12 weeks
Perceived risk of PREPS and cigarette evaluation
Measured: 12 weeks
Compensatory smoking
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2008 (estimated)
- Study startMar 2005
- Primary completionSep 2006
- Study completionNov 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Tobacco DependenceStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute on Drug Abuse (NIDA)
- Sponsor type
- US National Institutes of Health
- Collaborators
- National Cancer Institute (NCI)
- Investigators
- Dorohty Hatsukami, Ph.D., Principal investigator, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00777569
- Sponsor's protocol ID
- DA 013333
- Status last verified
- Dec 2008
- First submitted
- 21 Oct 2008
- Last updated
- 16 Jan 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Dermody SS, Donny EC, Hertsgaard LA, Hatsukami DK. Greater reductions in nicotine exposure while smoking very low nicotine content cigarettes predict smoking cessation. Tob Control. 2015 Nov;24(6):536-9. doi: 10.1136/tobaccocontrol-2014-051797. Epub 2014 Sep 5.
PubMed 25192771Hatsukami DK, Kotlyar M, Hertsgaard LA, Zhang Y, Carmella SG, Jensen JA, Allen SS, Shields PG, Murphy SE, Stepanov I, Hecht SS. Reduced nicotine content cigarettes: effects on toxicant exposure, dependence and cessation. Addiction. 2010 Feb;105(2):343-55. doi: 10.1111/j.1360-0443.2009.02780.x.
PubMed 20078491
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study 2: Comparisons of Nicotine-free Cigarettes, Extra Low Nicotine Cigarettes vs. Medicinal Nicotine
- ClinicalTrials.gov ID
- NCT00777569
- Acronym / sponsor ID
- DA 013333
- Conditions
- Tobacco Dependence
- Keywords
- Smoking, PREPS, Harm reduction, Biomarkers of tobacco exposure, Compensatory smoking
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- National Institute on Drug Abuse (NIDA)US National Institutes of Health
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Mar 2005
- Primary completion
- Sep 2006 (actual)
- Study completion
- Nov 2006 (actual)
- First posted
- 22 Oct 2008 (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.
In this study, smokers will be randomly assigned to one of three conditions for six weeks: 1) nicotine-free cigarettes (0.05mg); 2) extra low nicotine cigarettes (0.3 mg); or 3) medicinal 4 mg nicotine lozenge. The tobacco toxin profiles across these various products will be compared. The effects of these products on biomarkers of exposure and risk factors for disease, compensatory smoking, components of tobacco addiction and short-term smoking cessation will be determined. Predictors of response to these products (e.g., compensatory smoking, compliance with product use, time to lapse) will also be examined.
The following primary hypothesis will be tested: 1) Extent of tobacco toxin exposure will be greatest for the extra low nicotine cigarette and least for nicotine lozenge. Other secondary hypotheses include: 2) Compensatory smoking, as calculated by using cotinine, will be greatest for the extra low cigarette compared to the nicotine-free cigarette; 3) Greater positive subjective responses to cigarettes will be observed with extra low nicotine vs. nicotine-free cigarette; 4) Similar withdrawal symptoms and negative affect will be observed with nicotine-free cigarette and nicotine lozenge, and least withdrawal and negative affect with the extra low nicotine cigarette; 6) Least dependence and greatest motivation and self-efficacy to quit will be observed with nicotine lozenge and the greatest dependence and least motivation and self-efficacy to quit with the extra low nicotine cigarette use; 7) Shorter time to lapse will be observed with extra low nicotine vs. nicotine-free cigarettes because of extinction is likely to occur with nicotine-free cigarettes, and the longest time to lapse for nicotine lozenge because the cigarette condition groups will have experienced stronger attentional bias toward cues, and more dependence prior to the quit date and greater withdrawal after the quit date.
Detailed description
Smokers (N=150) will be enrolled in the study and will smoke ad libitum for a period of two weeks during which time they will be assessed for baseline measurements. Subjects will then be randomly assigned to one of the three conditions (N=50). Subjects will be blinded as to whether they are assigned to the Quest nicotine-free vs. extra low nicotine condition. There are no distinguishing features between these two cigarettes. Nicotine lozenge assignment is open label. Subjects will be asked to use only their assigned study product (low nicotine, nicotine-free cigarettes or lozenge) for a period of 6 weeks. Study cigarettes will be given to them at each clinic visit and subjects will be told to smoke ad libitum. They will be provided a supply equivalent to 150% of their baseline-smoking rate to allow for compensatory smoking to occur. They will keep record of each cigarette they smoked. If they smoked cigarettes other than those assigned to them, they will be asked to notate on a sheet when that cigarette was smoked. At the end of the 6-week period, they will be asked to quit smoking and NRT.
First morning urine and fasting blood samples will be collected at baseline and 2 and 6 weeks on the study products; at 6 weeks of abstinence and the 1 month follow-up.
Counseling. In each condition, subjects will be provided brief, structured counseling that is similar in duration. The subjects in the cigarette conditions will discuss any difficulties they experienced with switching cigarettes and problem solving these obstacles. Problem solving each obstacle will be solicited from the subject. However, if no solution or limited solution is provided, the counselor will provide a standardized response for each of the obstacles confronted.
Follow-up Phase. Subjects will be followed up 1 month after the end of the 6 week abstinence period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Extra-low nicotine cigarettes | Experimental | Drug: Extra-low nicotine cigarettes |
| Nicotine-free cigarettes | Experimental | Drug: Nicotine free cigarettes |
| Medicinal Nicotine | Active comparator | Drug: Nicotine Lozenge |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- smoking between 10-40 cigarettes daily for the past year;
- in good physical health (no unstable medical condition;
- no contraindications for medicinal nicotine;
- stable, good mental health
Key exclusion criteria (2 listed)
- unwilling to use study products for 6 weeks;
- unstable medical or psychiatric condition.
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 |
|---|---|---|
| Nicotine free cigarettesQuest Step 2 contains 0.05 mg nicotine | Drug | Nicotine-free cigarettes |
| Extra-low nicotine cigarettesQuest 2 cigarettes contains 0.3 mg nicotine | Drug | Extra-low nicotine cigarettes |
| Nicotine LozengeAlso: Commit4 mg nicotine lozenge | Drug | Medicinal Nicotine |
Primary outcome
Biomarkers for tobacco exposure measures: Carbon monoxide, cotinine, NNAL-gluc, NNN, mercapturic acids, 1-hydroxypytrene and biomarkers for cardiovascular risk: WBC, lipid profile, fibrinogen, heart rate, blood pressure.
Time frame: 6 weeks
Tobacco Cessation
Time frame: 12 weeks
5 secondary outcomes
Pulmonary function
Time frame: 12 weeks
Nicotine withdrawal symptoms
Time frame: 12 weeks
Motivation to quit and self-efficacy
Time frame: 12 weeks
Perceived risk of PREPS and cigarette evaluation
Time frame: 12 weeks
Compensatory smoking
Time frame: 6 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 16 Jan 2017.
- Derived from this study: PubMed 25192771Dermody SS, Donny EC, Hertsgaard LA, Hatsukami DK. Greater reductions in nicotine exposure while smoking very low nicotine content cigarettes predict smoking cessation. Tob Control. 2015 Nov;24(6):536-9. doi: 10.1136/tobaccocontrol-2014-051797. Epub 2014 Sep 5.
- Derived from this study: PubMed 20078491Hatsukami DK, Kotlyar M, Hertsgaard LA, Zhang Y, Carmella SG, Jensen JA, Allen SS, Shields PG, Murphy SE, Stepanov I, Hecht SS. Reduced nicotine content cigarettes: effects on toxicant exposure, dependence and cessation. Addiction. 2010 Feb;105(2):343-55. doi: 10.1111/j.1360-0443.2009.02780.x.
Related trials for Tobacco Dependence
Recruiting
Effectiveness of Volitional Help Sheets as an Adjunct to Treatment to Promote Behavior Change: A Pilot Study on Smoking
Tobacco Dependence
Recruiting
Young Adult Tobacco/Nicotine and Cannabis Co-use
Tobacco Use Disorder, Nicotine Dependence
Recruiting
Social Media Support Groups for Adolescent Vaping Cessation
Vaping, Vaping Cessation
Recruiting
The INITIATE Study: Initiating Nicotine Dependence Treatment for Smokers Admitted to Emergency Departments
Nicotine Dependence, Cigarettes, Nicotine Withdrawal
Recruiting
Advanced Functional and Structural MRI Techniques for Neuropharmacological Imaging
Drug Abuse, Nicotine Dependence
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.
Dorohty Hatsukami, Ph.D. principal investigator
University of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nicotine free cigarettes, Extra-low nicotine cigarettes and Nicotine Lozenge in people with Tobacco Dependence, run by National Institute on Drug Abuse (NIDA) at 1 site 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 4 inclusion and 2 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 16 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Biomarkers for tobacco exposure measures: Carbon monoxide, cotinine, NNAL-gluc, NNN, mercapturic acids, 1-hydroxypytrene and biomarkers for cardiovascular risk: WBC, lipid profile, fibrinogen, heart rate, blood pressure. (time frame: 6 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00777569, which also lists 2 linked publications.
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 16 Jan 2017.