Assessment of High Dose Transdermal Nicotine for Fast Metabolizers of Nicotine
Information source: University of Pennsylvania
Information obtained from ClinicalTrials.gov on October 04, 2010
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Nicotine Dependence
Intervention: Nicoderm CQ transdermal nicotine (Drug); placebo (Drug)
Phase: Phase 2
Status: Recruiting
Sponsored by: University of Pennsylvania Official(s) and/or principal investigator(s):
Robert A Schnoll, PhD, Principal Investigator, Affiliation: University of Pennsylvania
Overall contact:
Elisa Martinez, MPH, Phone: 215-746-3109, Email: emart@mail.med.upenn.edu
Summary
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.
Clinical Details
Official title: Assessment of High Dose Transdermal Nicotine for Fast Metabolizers of Nicotine
Study design: Allocation: Randomized, Control: Dose Comparison, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Biochemically verified 7-day point prevalence abstinence at the end of 8 weeks of treatment
Secondary outcome: Side effects
Detailed description:
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, 100 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.
Eligibility
Minimum age: 18 Years.
Maximum age: 45 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. Males and females age 18-45 who smoke > 10 cigarettes/ day;
2. Able to communicate in English;
3. Able to use NRT safely (e. g., no allergy to latex);
4. Able to provide written informed consent for study procedures;
5. Residing in the geographic area for at least 6 months; and
6. A 3-HC/cotinine ratio in the top quartile of the distribution (Schnoll et al., 2008).
Age 45 was selected as an upper limit to reduce the likelihood of adverse effects
from high dose transdermal nicotine.
Exclusion Criteria:
1. History of substance abuse or currently receiving treatment for substance abuse
(e. g., alcohol, opioids, cocaine, marijuana);
2. Current (last 6-months) alcohol consumption that exceeds 25 standard drinks/week.
3. Current use or discontinuation within last 14 days of:
- Smoking cessation medications (bupropion, Chantix, NRT);
- Antipsychotics, atypicals, mood-stabilizers, anti-depressants (tricyclics,
SSRIs, MAOIs), anti-panic agents, anti-obsessive agents, anti-anxiety agents,
stimulants);
- Medication for pain;
- Anti-coagulants;
- Heart medications;
- Daily medication for asthma or diabetes.
4. Women who are pregnant, planning a pregnancy, or lactating;
5. History or current diagnosis of psychosis, major depression or bipolar disorder,
psychotic disorder, or generalized anxiety disorder;
6. Serious/unstable disease within the past 6 months (e. g., cancer [but melanoma],
HIV/AIDS);
7. History of epilepsy or seizure disorder;
8. History or diagnosis within the last 6 months of abnormal rhythms and/or tachycardia
(>100 beats/minute); history or current diagnosis of COPD, cardiovascular disease
(stroke, angina), heart attack in the last 6 months, uncontrolled hypertension
(SBP>150 or DBP>90);
9. History of kidney or liver failure.
10. Any medical condition or medication that could compromise safety as determined by a
study physician;
11. Inability to provide informed consent or complete the study tasks as determined by
the Principal Investigator or study physician.
Locations and Contacts
Elisa Martinez, MPH, Phone: 215-746-3109, Email: emart@mail.med.upenn.edu
University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States; Recruiting
Elisa Martinez, MPH, Phone: 215-747-3109, Email: EMart@mail.med.upenn.edu
Additional Information
Starting date: August 2009
Last updated: September 21, 2010
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