OPTIMUM DOSE AND SCHEDULE FOR NICOTINE GUM TREATMENT

超过1万名美国人每人开出尼古丁口香糖的处方 天。自FDA三年前批准以来，约有100万患者(30%) 已经戒烟了，尽管医学博士S不知道 剂量(2毫克或4毫克)或服用口香糖的时间表(临时香烟 催促的或有规律的时间表，如清醒时的q1小时)是最多的 有效。尽管最近，NIDA的HIM实验室工作 ARC强烈表明在清醒状态下服用4毫克剂量q1小时 应该产生最好的治疗效果，这一假设还没有 经过临床测试。在拟议的研究中，我们计划确定 处理烟草的最佳尼古丁口香糖剂量和方案 依附性。我们将随机输入400名男性和女性 吸烟者进入2x2因子处理试验，交叉剂量(2vs 4 mg)加用药时间表(即刻vs q1h)。主题将是 分层，在随机分配到4个治疗中的1个之前 条件，按：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 (低依存度)&2)受试者是否曾经使用过 尼古丁口香糖2 mg。年龄、性别、吸烟史及其他 将控制可能影响治疗结果的因素 用于Logistic回归分析。在接受治疗后， 受试者将接受为期3个月的积极治疗，然后是4个月 逐渐缩减阶段。然后再对所有受试者进行12次追踪 莫以确定长期戒烟效果。这个 主要结果衡量标准将是持续禁欲。 香烟，客观地确认，在整个12个月内 通过随访结束逐渐缩小结束。其他受抚养人 在19个月的试验中测量的变量包括烟草 戒断症状，每天使用口香糖#，血清尼古丁& 可替宁，口香糖中残留的尼古丁量，以及情绪 国家，以及其他国家。我们将检查我们的数据以测试 假设：1)高依赖度吸烟者最好使用 4毫克剂量，每小时一次，但低依赖吸烟者最好使用 2毫克作为lib？2)在Fagerstrom尼古丁上有分数 耐受度预测最佳治疗条件？3)效果更好 戒烟治疗中戒烟症状的控制 提高戒烟率？4)在治疗过程中，血清可替宁水平更接近 当吸烟增加时戒烟的治疗方法？可以 受试者通过调节口香糖中尼古丁的摄入量来提高戒烟率？ 从这个项目中获得的知识应该会改善治疗结果 使用尼古丁口香糖，可以更好地匹配治疗和 主体条件，从而进一步减少数十亿美元， 卷烟引起的疾病每年的医疗费用。

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.