A Randomized Controlled Trial of Varenicline for Adolescent Smoking Cessation

描述(申请人提供)：吸烟是美国可预防死亡的主要原因，几乎普遍始于青春期。在这个特别脆弱的年龄段，吸烟者经常有戒烟的兴趣，但在自己尝试戒烟时很少成功。有鉴于此，并考虑到在很小的时候戒烟对健康的巨大好处，青少年戒烟的循证治疗是迫切需要的。令人惊讶的是，很少有研究解决这一需求，几乎所有的研究都集中在心理社会方法上，通常产生的治疗效果规模很小。虽然药物疗法在成年吸烟者中被公认为戒烟治疗，但在青少年吸烟者中只有6项对照试验的重点。尼古丁替代疗法和安非他酮SR的这些试验产生了喜忧参半的结果，但总体上是令人鼓舞的。Varenicline是一种42烟碱型乙酰胆碱受体部分激动剂，通过几项随机试验，与安慰剂、尼古丁替代疗法和安非他酮SR相比，它在成年人中显示出更好的戒烟效果。鉴于其作为成人戒烟治疗的显著疗效，varenicline是青少年吸烟者评估的有力候选者。根据一项青少年药代动力学研究的剂量建议和一项青少年试点戒烟试验的可行性/安全性信息，提出了一项用于青少年戒烟的随机、双盲安慰剂对照试验。参与者将被随机接受为期12周的varenicline或安慰剂治疗，并在治疗后进行多次随访，持续6个月。每周一次的精神和医疗检查，包括详细、严格的安全性/耐受性评估，将在整个积极治疗过程中进行。所有参与者将同时参加应急管理干预，旨在提高研究保持率。主要的疗效假设是，与那些接受安慰剂的参与者相比，接受varenicline治疗的参与者在治疗结束时将表现出更大的生物确认的7天点戒毒盛行率。我们进一步假设，与安慰剂相比，在治疗出现的不良事件的频率上，有足够的安全性和耐受性。这项拟议的研究将填补一个关键的证据空白，并有可能显著推进青少年戒烟治疗。无论研究结果是肯定的、无效的还是否定的，这都将是对文献的重要贡献，并将对临床和公共卫生产生重大影响。

DESCRIPTION (provided by applicant): Cigarette smoking, the leading cause of preventable death in the United States, almost universally begins in adolescence. Smokers in this especially vulnerable age group are often interested in quitting, but are rarely successful when making quit attempts on their own. In light of this, and given the considerable health benefit of quitting smoking at a young age, evidence-based treatments for adolescent smoking cessation are critically needed. Surprisingly little research has addressed this need, and almost all of it has focused on psychosocial approaches, yielding generally small treatment effect sizes. Pharmacotherapy, while well established as a cessation treatment in adult smokers, has been the focus of only 6 controlled trials in adolescent smokers. These trials of nicotine replacement therapy and bupropion SR have produced mixed but generally encouraging results. Varenicline, a 42 nicotinic acetylcholine receptor partial agonist, has demonstrated superior cessation efficacy in adults across several randomized trials when compared to placebo, nicotine replacement therapy, and bupropion SR. Given its striking efficacy as an adult smoking cessation treatment, varenicline is a strong candidate for evaluation in adolescent smokers. Guided by dosing recommendations from an adolescent pharmacokinetic study and feasibility/safety information from an adolescent pilot cessation trial, a randomized, double blind placebo-controlled trial of varenicline for adolescent smoking cessation is proposed. Participants will be randomized to receive varenicline or placebo for 12 weeks, with multiple post-treatment follow-up visits through 6 months. Weekly psychiatric & medical visits, including detailed, rigorous safety/tolerability assessment, will be conducted throughout active treatment. All participants will concurrently participate in a contingency management intervention, designed to enhance study retention. The primary efficacy hypothesis is that participants receiving varenicline, compared with those receiving placebo, will demonstrate greater biologically confirmed 7-day point prevalence abstinence at the end of treatment. We further hypothesize adequate safety and tolerability, compared with placebo, in the frequency of treatment-emergent adverse events. The proposed study will fill a critical evidence gap, and has the potential to significantly advance adolescent smoking cessation treatment. Whether findings are positive, null, or negative, this will be an important contribution to the literature and will have considerale clinical and public health impact.