OPTIMUM DOSE AND SCHEDULE FOR NICOTINE GUM TREATMENT

超过10，000名美国人填写尼古丁口香糖处方 天 自3年前FDA批准以来，约有100万患者（30%） 已经戒烟了，尽管医学博士。不知道什么 剂量（2毫克或4毫克）或什么时间表采取口香糖（自由吸烟 敦促或定期的时间表，例如，q1 h而清醒）是最 有效 虽然最近，来自NIDA的人类实验室工作 ARC强烈表明，清醒时每隔1小时服用4 mg剂量 应该产生最好的治疗效果，这种假设没有 经过临床测试。 在拟议的研究中，我们计划确定 治疗烟草的最佳尼古丁口香糖剂量和时间表 依赖 我们将随机抽取400名男性和女性 吸烟者进入2x2析因治疗试验，交叉剂量（2 vs 4 mg）与药物治疗方案（自由相对于q1 h）。 受试者将 分层，随机分配至4种治疗之一前 1）基线，吸烟可替宁水平： 大于294 ng/ml（高度依赖）或小于294 ng/ml (Low（2）是否曾经使用过 2 mg尼古丁口香糖。 年龄、性别、吸烟史及其他 控制可能影响治疗结果的因素 在logistic回归分析中。 在药物摄入后， 受试者将接受3个月的活性治疗，随后接受4个月的活性治疗 渐缩阶段。 然后所有受试者将再接受12次随访 以确定长期戒烟的结果。 的 主要的结果指标将是持续的禁欲， 香烟，客观证实，从整个12个月， 逐渐减少结束至随访结束。 其他未独立 在整个19个月试验中测量的变量包括烟草 戒断症状，每天使用的口香糖数量，血清尼古丁和 可替宁，口香糖中残留的尼古丁量，以及情绪 国家，除其他外。 我们将检查我们的数据， 假设：1）高依赖性吸烟者最好用 4 mg剂量q1 h，但低依赖性吸烟者最好用 2 mg作为lib？ 2)在Fagerstrom尼古丁上得分 耐受性量表预测最佳治疗条件？ 3)做得更好 在治疗期间控制烟草戒断症状 提高戒烟率？ 4)是否更接近匹配的血清可替宁在 吸烟增加戒烟时的治疗方法？ 5)可以 受试者控制从口香糖中摄入尼古丁以提高戒烟率？ 从这个项目中获得的知识应该可以改善治疗效果 与尼古丁口香糖，允许更好地匹配治疗和 受条件限制，从而进一步减少数十亿美元， 每年的医疗费用由香烟引起的疾病。

Over 10,000 Americans fill prescriptions for nicotine gum each day. Since FDA approval 3 yr ago, about 1 million patients (30%) have stopped smoking with it, despite M.D.'s not knowing what dose (2mg or 4mg) or what schedule of taking gum (ad lib cigarette urge or on a regular time schedule, eg, q1h while awake) is most effective. Although recent, hman laboratory work from the NIDA ARC strongly indicates that a 4mg dose taken q1h while awake should produce the best treatment results, this hypothesis has not been clinically tested. In the proposed study we plan to determine the optimal nicotine gum dose & schedule to treat tobacco dependency. We shall randomly enter 400 male and female smokers into a 2x2 factorial treatment trial, crossing dose (2 vs 4mg) with medication schedule (ad lib vs q1h). Subjects will be stratified, before random assignment to 1 of 4 treatment conditions, by: 1) Baseline, cigarette smoking cotinine level: greater than 294 ng/ml (High dependent) or less than 294 ng/ml (Low dependent) & 2) Whether or not the subject has ever used 2mg nicotine gum before. Age, sex, smoking history, & other factors which could influence treatment results will be controlled for in the logistic regression analysis. After medical intake, subjects will be in Active Treatment for 3 mo followed by a 4 mo Tapering Phase. Then all subjects will be followed for 12 more mo to determine long-term smoking cessation results. The primary outcome measure will be sustained abstinence from cigarettes, objectively confirmed, for the entire 12 mo from the end of Tapering through the end of Follow-Up. Other dependent variables measured throughout the 19 mo trial include tobacco withdrawal symptoms, # gums used/day, serum nicotine & cotinine, amount of nicotine remaining in chewed gum, & mood state, among others. We shall examine our data to test the hypotheses: 1) Are high dependent smokers best treated with a 4mg dose taken q1h, but low dependent smokers best treated with 2mg taken as lib? 2) Does score on the Fagerstrom Nicotine Tolerance Scale predict best treatment condition? 3) Does better control of tobacco withdrawal symptoms during treatment increase quit rate? 4) Does closer match of serum cotinine during treatment to that when smoking increase quitting? 5) Can subjects regulate nicotine intake from gum to improve quit rate? Knowledge from this project should improve treatment results with nicotine gum, allowing better matching of treatment & subject conditions, thus further reducing the multibillion dollar, annual medical costs of cigarette produced diseases.