A Randomized Controlled Trial of Varenicline for Adolescent Smoking Cessation

描述（由申请人提供）：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组的吸烟者往往有兴趣戒烟，但很少成功地尝试戒烟自己。鉴于此，并考虑到年轻时戒烟的巨大健康益处，青少年戒烟的循证治疗是至关重要的。令人惊讶的是，很少有研究解决了这一需求，几乎所有的研究都集中在心理社会方法上，产生的治疗效果通常很小。药物治疗虽然已被公认为成年吸烟者的戒烟治疗，但仅在青少年吸烟者中进行了6项对照试验。这些尼古丁替代疗法和安非他酮SR的试验产生了混合但总体上令人鼓舞的结果。 伐尼克兰是一种42烟碱乙酰胆碱受体部分激动剂，在几项随机试验中，与安慰剂、尼古丁替代疗法和安非他酮SR相比，伐尼克兰在成人中表现出上级戒烟疗效。鉴于其作为成人戒烟治疗的显著疗效，伐尼克兰是青少年吸烟者评估的有力候选者。 根据青少年药代动力学研究的剂量建议和青少年初步戒烟试验的可行性/安全性信息，提出了一项关于伐尼克兰用于青少年戒烟的随机、双盲、安慰剂对照试验。参与者将随机接受伐尼克兰或安慰剂治疗12周，并在6个月内进行多次治疗后随访。在整个积极治疗期间，将进行每周一次的精神病和医学访视，包括详细、严格的安全性/耐受性评估。所有受试者将同时参加旨在提高研究保留率的应急管理干预。 主要有效性假设是，与接受安慰剂的受试者相比，接受伐尼克兰的受试者在治疗结束时将表现出更高的生物学证实的7天点戒烟率。我们进一步假设与安慰剂相比，在治疗后出现的不良事件的频率方面具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，并有可能显着推进青少年戒烟治疗。无论结果是阳性、无效还是阴性，这都将是对文献的重要贡献，并将产生重大的临床和公共卫生影响。

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.