A Phase 2 interventional study of Nicoderm CQ transdermal nicotine and placebo in Nicotine Dependence, sponsored by University of Pennsylvania. Completed at 1 site in United States. Open to participants aged 18 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2014-08-15.
Sponsored by University of Pennsylvania · Phase 2, Interventional, and Treatment
Unfortunately, the investigators still need to assess and identify novel ways to help people quit smoking. Differences between people in terms of how fast they metabolize nicotine influences response to transdermal nicotine patches, the most popular nicotine dependence treatment, and it affects plasma levels of nicotine from treatment. These studies suggest that fast metabolizers of nicotine may show better quit rates if they receive higher doses of transdermal nicotine. This preliminary study is designed to assess, for the first time, whether fast nicotine metabolizers show higher quit rates if given high dose transdermal nicotine, versus standard dose. The study findings may help to support a subsequent large trial to assess standard versus high dose transdermal nicotine for slow versus fast metabolizers of nicotine, which may lead to a more personalized approach to treating nicotine dependence using the nicotine patch to improve therapeutic benefits of transdermal nicotine.
Novel approaches to treating nicotine dependence remain a priority. The transdermal nicotine patch is the most widely used form of tobacco dependence treatment, but only \~1 in 5 smokers who use this treatment achieve cessation. One factor that may contribute to a poor response to transdermal nicotine is inter-individual variability in the rate of nicotine metabolism, which can be measured in saliva by the ratio of 3'hydroxycotinine (3-HC) to its precursor cotinine.
Two clinical trials with transdermal nicotine have shown that the 3-HC/cotinine ratio predicts response to transdermal nicotine such that faster metabolizers of nicotine (higher 3-HC/cotinine ratios) have lower quit rates, vs. slower nicotine metabolizers. Among abstainers in these trials, the 3-HC/cotinine ratio also predicts therapeutic levels of nicotine on transdermal nicotine, with faster metabolizers of nicotine exhibiting lower nicotine. Thus, faster metabolizers of nicotine may require higher nicotine doses to achieve the same therapeutic benefit from transdermal nicotine as do slow nicotine metabolizers.
To date, clinical trials have shown that, compared to the standard dose of transdermal nicotine (21mg), higher doses (42mg) have no significant effect on quit rates. However, no trial of high dose transdermal nicotine considered inter-individual variability in the rate of nicotine metabolism. Thus, as a preliminary step toward conducting a fully-powered, randomized clinical trial to assess standard vs. high dose transdermal nicotine for slow vs. fast metabolizers of nicotine, we propose to evaluate, for the first time, the efficacy of high-dose transdermal nicotine (vs. standard dose) among fast metabolizers of nicotine (i.e., upper quartile of the 3-HC/cotinine ratio distribution).
We chose only fast metabolizers of nicotine for this trial since: 1) slow metabolizers of nicotine exhibit high quit rates on standard transdermal nicotine and may experience adverse effects from higher doses; and 2) as a "proof of concept" R21 application, our primary objective is to test whether high doses of nicotine increase quit rates among fast metabolizers of nicotine. Specifically, smokers who are fast metabolizers of nicotine will receive counseling and will be randomized to: 1) standard (1 X 21mg patch and 1 X placebo patch), or 2) high dose (2 x 21mg patches) transdermal nicotine.
The primary outcome is biochemically-verified 7-day point prevalence cessation after 8 weeks of treatment. Differences in patch-related side effects and mediators of transdermal nicotine effects (e.g., nicotine levels, withdrawal) across the study conditions will also be assessed.
Ultimately, this line of research hopes to provide the evidence necessary to translate research on the 3-HC/cotinine ratio to clinical practice for the treatment of tobacco dependence. Specifically, this research may show that a measure of nicotine metabolism rate could be used to maximize the therapeutic benefits of transdermal nicotine by providing slow metabolizers of nicotine with a standard patch dose and fast metabolizers of nicotine with high dose transdermal nicotine. Identifying an effective treatment for faster metabolizers of nicotine is also critical since these individuals are at increased risk for lung cancer.
968 studies on the registry are indexed under Tobacco Use Disorder; 126 are open to participants now.
This study's enrollment of 87 is close to the median of 89 across 851 interventional studies indexed under Tobacco Use Disorder.
Browse Tobacco Use Disorder studies →University of Pennsylvania is the lead sponsor of 1,635 studies on the registry; 239 are open to participants now.
Of its 154 completed or terminated interventional studies of FDA-regulated products, 104 (68%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Current use or discontinuation within last 14 days of:
21mg transdermal nicotine + placebo patch
Drug: Nicoderm CQ transdermal nicotine · Drug: placebo
42mg transdermal nicotine
Drug: Nicoderm CQ transdermal nicotine
Transdermal nicotine patch (21mg vs. 42mg), 8 weeks
placebo patch
Biochemically Verified 7-day Point Prevalence Abstinence at the End of 8 Weeks of Treatment
quit rate verified with carbon monoxide breath sample (abstinence: less than or equal to 10ppm)
Time frame: After 8 weeks of treatment with the patch, outcome will be measured.
Side Effects
frequency of serious adverse events
Time frame: 8 weeks
Media ads asked treatment-seeking smokers to call for information about a smoking cessation program and to have their initial eligibility reviewed. Participants interested in the clinical trial and initially eligible attended an in-person session to determine their final eligibility. Recruitment was from 2009-2011.
| Milestone | 21mg Transdermal Nicotine + Placebo Patch | 42mg Transdermal Nicotine |
|---|---|---|
| Started | 43 | 44 |
| Baseline | 43 | 44 |
| Completed | 34 | 34 |
| Not completed | 9 | 10 |
| Withdrew: Lost to follow-up | 9 | 10 |
quit rate verified with carbon monoxide breath sample (abstinence: less than or equal to 10ppm)
| participants | 21mg Transdermal Nicotine + Placebo Patch | 42mg Transdermal Nicotine |
|---|---|---|
| Biochemically Verified 7-day Point Prevalence Abstinence at the End of 8 Weeks of Treatment | 10 | 13 |
frequency of serious adverse events
| events | 21mg Transdermal Nicotine + Placebo Patch | 42mg Transdermal Nicotine |
|---|---|---|
| Side Effects | 0 | 1 |
Collected over 8 weeks. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| 21mg Transdermal Nicotine + Placebo Patch | — | 0/43 (0%) | 0/43 (0%) |
| 42mg Transdermal Nicotine | — | 1/44 (2.3%) | 0/44 (0%) |
| Event | 21mg Transdermal Nicotine + Placebo Patch | 42mg Transdermal Nicotine |
|---|---|---|
| influenzaInfections and infestations | 0/43 | 1/44 |
| Age, Categorical(Participants) | 21mg Transdermal Nicotine + Placebo Patch | 42mg Transdermal Nicotine | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 43 | 44 | 87 |
| >=65 years | 0 | 0 | 0 |
| Age, Continuous(years) | 21mg Transdermal Nicotine + Placebo Patch | 42mg Transdermal Nicotine | Total |
|---|---|---|---|
| Mean | 37.1 ± 9.0 | 38.8 ± 9.0 | 38 ± 9 |
| Sex: Female, Male(Participants) | 21mg Transdermal Nicotine + Placebo Patch | 42mg Transdermal Nicotine | Total |
|---|---|---|---|
| Female | 22 | 23 | 45 |
| Male | 21 | 21 | 42 |
| Region of Enrollment(participants) | 21mg Transdermal Nicotine + Placebo Patch | 42mg Transdermal Nicotine | Total |
|---|---|---|---|
| United States | 43 | 44 | 87 |
This study is completed, as verified in Aug 2014. You cannot join it, but the record below documents what was studied.
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University of Pennsylvania