Efficacy of Varenicline for Smokless Tobacco Use in India

描述（由申请人提供）：与吸烟相比，美国无烟烟草的使用率较低。然而，在过去几年里，吸烟率一直保持不变，烟草公司最近推出了新的无烟烟草产品，作为戒烟辅助工具，或者作为在室内公共场所禁止吸烟的替代品。相比之下，印度的无烟烟草使用率为20%。无烟烟草具有致癌性，每年在印度造成约1万人死于口腔癌。不幸的是，印度针对无烟烟草使用者的干预试验非常少。在美国，尼古丁替代疗法（nrt）和安非他酮的临床试验没有发现任何结果。到目前为止，还没有试验评估FDA批准的选择性1422神经元烟碱乙酰胆碱受体部分激动剂伐尼克兰用于无烟烟草的使用。因此，拟议的国际合作研究将加强位于新德里全印度医学研究所的国家药物依赖治疗中心（NDDTC）的研究能力，并对位于新德里的NDDTC的250名无烟烟草使用者进行伐尼克兰治疗无烟烟草依赖的随机安慰剂对照试验。该试验的主要目的是：1)提高NDDTC的研究能力（即培训和监督AIIMS工作人员实施带有药物治疗、数据收集和管理程序以及参与者跟踪系统的行为咨询协议）；2)评估伐尼克兰对提高治疗结束时经生化证实的7天点流行无烟烟草戒烟率的疗效；2)评估伐尼克兰治疗后复发和恢复的纵向模式。本试验还将探讨：1)戒断症状、渴望、情感和无烟烟草的享乐效应的变化作为伐尼克兰效应的机制；2)与无烟烟草相关的（例如，无烟烟草的持续时间和类型）、心理（例如，抑郁）和人口统计学（例如，性别）变量对伐尼克兰反应的作用，以确定最有可能从伐尼克兰获益的无烟烟草依赖者。我们建议在印度进行这项临床试验是因为：1)无烟烟草的使用在印度是一个重大的公共卫生问题；2)印度没有进行无烟烟草使用的药物治疗试验；3)参与者招募将具有成本效益；4)我们可以评估瓦伦克林效应的广泛调节因子（例如，性别）。这项研究的结果可能支持一项R01试验，以评估长期治疗效果和其他目标，如成本效益和向决策者和提供者传播结果的机制。拟议的研究也可能为美国无烟烟草使用者提供重要信息，因为：1)美国无烟烟草的使用最近保持不变，并可能在未来几年增加；2) NRT和安非他酮对无烟烟草依赖无效；3)伐尼克兰尚未被评价为一种治疗无烟烟草使用的方法。

DESCRIPTION (provided by applicant): The prevalence of smokeless tobacco use in the US is low vs. cigarette smoking. Yet, rates have remained constant over the past few years, and tobacco companies recently launched new smokeless tobacco products as smoking cessation aids or as alternatives to smoking given bans on smoking in indoor public places. In contrast, the rate of smokeless tobacco use in India is 20%. Smokeless tobacco is carcinogenic and responsible for ~10,000 deaths/year from oral cancer in India. Unfortunately, there have been remarkably few intervention trials in India for smokeless tobacco users. In the US, clinical trials of nicotine replacement therapies (NRTs) and bupropion have yielded null findings. To date, no trial has evaluated the new FDA- approved selective 1422 neuronal nicotinic acetylcholine receptor partial agonist, varenicline, for smokeless tobacco use. Thus, the proposed international collaborative study would enhance research capacity at the National Drug Dependence Treatment Center (NDDTC) at the All India Institute of Medicine in New Delhi and conduct a randomized placebo-controlled trial of varenicline for smokeless tobacco dependence with 250 smokeless tobacco users at the NDDTC in New Delhi. The primary aims of this trial are to: 1) enhance research capacity at the NDDTC (i.e., train and supervise AIIMS staff to implement the behavioral counseling protocol with pharmacotherapy, data collection and management procedures, and participant tracking systems); 2) assess the efficacy of varenicline for increasing biochemically confirmed 7-day point prevalence smokeless tobacco quit rates at the end-of-treatment; and 2) assess longitudinal patterns of relapse and recovery following treatment with varenicline. This trial will also explore: 1) changes in withdrawal symptoms, craving, affect, and hedonic effects of smokeless tobacco as mechanisms of varenicline effects; and 2) the role of smokeless tobacco-related (e.g., duration and type of smokeless tobacco), psychological (e.g., depression), and demographic (e.g., gender) variables on response to varenicline to identify those most likely to benefit from varenicline for smokeless tobacco dependence. We propose this clinical trial in India since: 1) smokeless tobacco use is a substantial public health problem in India; 2) no pharmacotherapy trials for smokeless tobacco use have been conducted in India; 3) participant recruitment will be cost-effective; and 4) we can assess a broad range of moderators of varenicline effects (e.g., gender). The results from this study may support an R01 trial to evaluate long-term treatment effects and additional aims such as cost-effectiveness and mechanisms for the dissemination of results to policy-makers and providers. The proposed study may also yield important information for US smokeless tobacco users since: 1) smokeless tobacco use in the US has remained constant recently and may increase in the coming years; 2) NRT and bupropion are ineffective for smokeless tobacco dependence; and 3) varenicline has not been evaluated as a treatment for smokeless tobacco use. PUBLIC HEALTH RELEVANCE: The prevalence of smokeless tobacco use in the US is ~3%, which is far lower than for cigarette smoking. Yet, rates have remained constant over the past few years, and tobacco companies recently launched new smokeless tobacco products as smoking cessation aids or as alternatives to smoking given bans on smoking in indoor public places. In contrast, the rate of smokeless tobacco use in India is 20%. To date, no pharmacotherapy has demonstrated efficacy for smokeless tobacco use in US trials, no pharmacotherapy trials for smokeless tobacco use have been conducted in India, and no clinical trial has evaluated the new FDA- approved medication for tobacco smoke, varenicline, for smokeless tobacco use. Thus, the proposed international collaborative study would enhance research capacity at the National Drug Dependence Treatment Center (NDDTC) at the All India Institute of Medicine in New Delhi and conduct a randomized placebo- controlled trial of varenicline for smokeless tobacco dependence at the NDDTC in New Delhi. The results from this trial will fill several important gaps in the empirical literature, address significant public health concerns for India and the US, and facilitate additional research studies in India.