Assessment of High Dose Transdermal Nicotine for Fast Metabolizers of Nicotine
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 87
- 试验地点
- 1
- 主要终点
- Biochemically Verified 7-day Point Prevalence Abstinence at the End of 8 Weeks of Treatment
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Males and females age 18-45 who smoke > 10 cigarettes/ day;
- •Able to communicate in English;
- •Able to use NRT safely (e.g., no allergy to latex);
- •Able to provide written informed consent for study procedures;
- •Residing in the geographic area for at least 6 months; and
- •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.
排除标准
- •History of substance abuse or currently receiving treatment for substance abuse (e.g., alcohol, opioids, cocaine, marijuana);
- •Current (last 6-months) alcohol consumption that exceeds 25 standard drinks/week.
- •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.
- •Women who are pregnant, planning a pregnancy, or lactating;
- •History or current diagnosis of psychosis, major depression or bipolar disorder, psychotic disorder, or generalized anxiety disorder;
- •Serious/unstable disease within the past 6 months (e.g., cancer [but melanoma], HIV/AIDS);
- •History of epilepsy or seizure disorder;
- •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);
- •History of kidney or liver failure.
- •Any medical condition or medication that could compromise safety as determined by a study physician;
- •Inability to provide informed consent or complete the study tasks as determined by the Principal Investigator or study physician.
研究组 & 干预措施
21mg transdermal nicotine + placebo patch
21mg transdermal nicotine + placebo patch
干预措施: Nicoderm CQ transdermal nicotine (Drug)
21mg transdermal nicotine + placebo patch
21mg transdermal nicotine + placebo patch
干预措施: placebo (Drug)
42mg transdermal nicotine
42mg transdermal nicotine
干预措施: Nicoderm CQ transdermal nicotine (Drug)
结局指标
主要结局
Biochemically Verified 7-day Point Prevalence Abstinence at the End of 8 Weeks of Treatment
时间窗: After 8 weeks of treatment with the patch, outcome will be measured.
quit rate verified with carbon monoxide breath sample (abstinence: less than or equal to 10ppm)
次要结局
- Side Effects(8 weeks)
研究者
Robert Schnoll
Associate Professor
University of Pennsylvania