Track topics on Twitter Track topics that are important to you
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, 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.
Allocation: Randomized, Control: Dose Comparison, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Nicoderm CQ transdermal nicotine, placebo
University of Pennsylvania
University of Pennsylvania
Published on BioPortfolio: 2014-08-27T03:20:08-0400
The transdermal nicotine patch is the most widely used form of tobacco dependence treatment in the US and Europe, but most smokers are unable to successfully quit with this form of treatme...
This study is designed to evaluate the initial evidence for efficacy of the investigational medicine, EVP-6124, to improve smoking cessation outcomes with and without a standard taper of n...
This study examines the effect of combined nicotine replacement therapy (transdermal patch + nasal spray vs. transdermal patch + placebo nasal spray) on reactivity to alcohol and self-admi...
Smoking while on nicotine patches will help subjects to reduce their expired carbon monoxide levels from the levels they were before they started using the patch. Subjects will also decrea...
The primary objective of this study is to determine which is the better approach to smoking cessation in veterans: bupropion combined with transdermal nicotine or high dose nicotine replac...
Nicotine dependence during adolescence increases the risk of continuing smoking into adulthood. The magnitude of nicotine dependence among adolescents in the European Union (EU) has not been establish...
Adolescent e-cigarette use (i.e., "vaping") likely confers risk for developing nicotine dependence. However, there have been no studies assessing e-cigarette nicotine dependence in youth. We evaluated...
Nicotine replacement therapy in the form of transdermal nicotine patches and nicotine gums combined with behavioral counseling still has a low smoking cessation rate of 25%. A promising approach to sm...
Nicotine addiction is the proximate cause of disease and death from cigarette smoking. In 1994, we proposed reducing the nicotine content of cigarettes to non-addicting levels to reduce the risk of yo...
Identify correlates of nicotine dependence [lifetime (l) and ongoing (o)] in adults with attention-deficit/hyperactivity disorder (ADHD) in childhood. We conducted a 33-year prospective follow-up of b...
Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.
Chewing gum which contains NICOTINE.
SMOKING vapors produced from ELECTRONIC NICOTINE DELIVERY SYSTEMS.
A plant genus of the family SOLANACEAE. Members contain NICOTINE and other biologically active chemicals; its dried leaves are used for SMOKING.
The N-glucuronide conjugate of cotinine is a major urinary metabolite of NICOTINE. It thus serves as a biomarker of exposure to tobacco SMOKING. It has CNS stimulating properties.
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells. In vertebrates, it is composed of blo...
In a clinical trial or interventional study, participants receive specific interventions according to the research plan or protocol created by the investigators. These interventions may be medical products, such as drugs or devices; procedures; or change...
Lung cancer is the uncontrolled cell growth in tissues of the lung. Originating in the lungs, this growth may invade adjacent tissues and infiltrate beyond the lungs. Lung cancer, the most common cause of cancer-related death in men and women, is respons...