Naltrexone Treatment

描述（由申请人提供）：在这项国际试点研究中，我们使用来自海洛因依赖治疗的四项临床试验的数据，以确定哪些患者将是纳洛酮治疗的更好应答者，以及在应答者中哪种类型的纳洛酮制剂（口服，植入或注射）导致最佳结果。虽然在美国，纳洛酮已被FDA批准用于治疗阿片类药物成瘾，但它尚未得到充分利用。在俄罗斯（替代疗法是非法的），纳洛酮是唯一的药物治疗选择。纳洛酮有三种形式：口服和缓释、注射和植入式贮库制剂。一种新的方法（基于模型的随机森林，mobForest）（Garge et al. 2013）将扩展到海洛因治疗和单一可解释的简约模型的开发。这些方法将应用于过去四项纳洛酮疗效随机双盲、双模拟、安慰剂对照临床试验的组合数据，并确定哪些患者可能对不同的纳洛酮制剂有反应。这些研究在俄罗斯的彼得堡进行，有近1,000名患者的数据，涉及人口统计学、临床、遗传学和心理测量学领域的400多个个体水平变量。我们将开发有效的预测模型，提供患者反应的预后。我们将为跨文化临床实践提供临床相关解释，并评估在更大规模的多国研究中的潜在用途。

DESCRIPTION (provided by applicant): In this international pilot study we use data from four clinical trials of heroin dependence treatment to identify which patients will be better respondents to naltrexone treatment and among respondents which type of naltrexone formulation (oral, implantable, or injectable) leads to the best outcome. Although in the United States naltrexone has been FDA approved for treatment of opioid addiction it has been underutilized. In Russia (where substitution therapy is illegal), naltrexone is the only pharmacological treatment option. Naltrexone is available in three forms: oral and extended release, injectable, and implantable depot-formulations. A novel methodology (Model-based Random Forest, mobForest) (Garge et al. 2013) will be extended to heroin treatment and to the development of a single interpretable parsimonious model. These methods will be applied to combined data from past four naltrexone efficacy randomized double blind, double dummy, placebo- controlled clinical trials and identify which patients are likely to respond to different naltrexone formulations. These studies were conducted in St. Petersburg, Russia, have data on almost 1,000 patients with more than 400 individual-level variables spanning demographics, clinical, genetic, and psychometrics domains. We will develop validated predictive models that provide prognosis of patients' response. We will provide clinically- relevant interpretations to cross-cultural clinical practice, and assess potential use in a larger multi-country study.