Short-term Outcome of Stimulant Use Disorder Treatment Trials

兴奋剂使用障碍治疗试验的短期结果

• 批准号: 10671072
• 负责人: RAMIN MOJTABAI
• 金额: $ 40.94万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10671072
• 关键词: Abstinence; Age; American; Baclofen; Bupropion; Characteristics; Chronic; Clinical; Clinical Treatment; Clinical Trials Network; Cocaine; Cocaine use disorder; Combination Medication; Combined Modality Therapy; Complex; Data; Dependence; Distress; Dropout; Drug usage; Effectiveness; Epidemic; Equilibrium; Ethnic Origin; Evaluation; FDA approved; Fatality rate; Frequencies; Future; Health; Heterogeneity; Individual; Measures; Mediating; Mediator; Methamphetamine; Methamphetamine use disorder; Modafinil; Naltrexone; National Institute of Drug Abuse; Nicotine Use Disorder; Ondansetron; Opioid; Outcome; Overdose; Participant; Patient Participation; Patients; Pattern; Persons; Pharmaceutical Preparations; Pharmacological Treatment; Phase; Probability; Property; Publications; Race; Randomized, Controlled Trials; Recurrence; Relapse; Research; Reserpine; Role; Sample Size; Sampling; Selegiline; Severities; Signal Transduction; Stimulant; Structural Models; Subgroup; Substance Use Disorder; Substance Withdrawal Syndrome; Symptoms; Techniques; Treatment outcome; Variant; Withdrawal; Withdrawal Symptom; alcohol abuse therapy; alcohol craving; alcohol use disorder; analytical method; behavioral phenotyping; cabergoline; candidate identification; clinically relevant; comorbidity; craving; data harmonization; depressive symptoms; drug craving; drug relapse; drug seeking behavior; experience; follow-up; morphogens; nicotine craving; nicotine treatment; novel; patient subsets; prolonged abstinence; psychological distress; response; sex; social; standard of care; stimulant misuse; stimulant use; stimulant use disorder; stimulant user; substance use; tiagabine; topiramate; treatment effect; treatment trial

Project Summary Stimulant use disorders, including cocaine and methamphetamine use disorders, impact the lives of millions of Americans and are associated with significant health and social consequences. There are currently no FDA- approved medications for treatment of stimulant use disorders. Most of the randomized controlled trials (RCTs) to find effective medications have been of short duration, typically lasting 8-12 weeks, and had small sample sizes. Attaining sustained abstinence from stimulants may require longer treatment and detecting these effects may require larger samples. However, available trials can provide information on short-term outcomes of treatment that are achieved earlier and less stringent than abstinence and, thus, help identify candidate medications for future long-term and larger trials. Drug craving is probably the most promising of such short- term outcomes. Stimulant use disorders are characterized by periods of heavy use followed by short periods of abstinence with withdrawal symptoms. These symptoms last a few days and are followed by increasing drug craving which often leads to relapse. Drug craving is a central phenomenon in these recurring cycles of drug use. Nevertheless, little research has specifically focused on craving as an outcome of stimulant use disorder or on reduction of craving as a mediator of abstinence or reduction in drug use. In the proposed project, we plan to examine craving as an outcome of stimulant use disorder as well as a mediator for other outcomes. More specifically, in Aim 1, we will compare the effect of 9 medications (in 11 RCTs) on stimulant drug craving. In Aim 2, we will assess the association of change in craving during trial with change in other outcomes and the potential mediating role of craving in the effect of treatments on these outcomes. In Aim 3 we will explore the variations in the effects of medications and in the association of craving with other outcomes in subgroups of patients. We propose to use individual participant data from 1,845 patients in 11 RCTs conducted in the context of NIDA’s Clinical Trials Network (CTN) and related trials to accomplish these study Aims. The project has the potential to significantly contribute to a better understanding of the role of craving in continued stimulant use disorder and the potential effect of medications on stimulant use disorders as mediated by their anti-craving qualities. Medications with anti-craving properties are currently used in treatment of nicotine and alcohol use disorders and have shown promising results in treatment of stimulant use disorders. The project also represents an efficient use of NIDA’s RCT data to answer new questions that were not addressed in the original studies. The findings would help identify candidate medications for future adequately powered trials based on the short-term anti-craving effects of candidate medications and contribute significantly to the ongoing efforts to find effective medication treatments for stimulant use disorders.

项目摘要 兴奋剂使用障碍，包括可卡因和甲基苯丙胺使用障碍，影响数百万人的生活 并与重大的健康和社会后果有关。目前没有FDA- 经批准的治疗兴奋剂使用障碍的药物。大多数随机对照试验(RCT) 寻找有效药物的持续时间很短，通常持续8-12周，而且样本很少 大小。要实现对兴奋剂的持续戒断，可能需要更长的治疗时间并检测到这些影响 可能需要更大的样本。然而，可用的试验可以提供关于以下方面的短期结果的信息 比禁欲更早且不那么严格的治疗，从而有助于确定候选人 用于未来长期和更大规模试验的药物。毒瘾可能是这类短片中最有希望的- 期限结果。兴奋剂使用障碍的特征是先是大量使用，然后是短暂的 戒酒并伴有戒断症状。这些症状会持续几天，之后药物会增加。 经常导致旧病复发的渴望。在这些反复出现的药物循环中，药物渴求是一个中心现象 使用。然而，很少有研究专门将渴望作为兴奋剂使用障碍的结果。 或关于减少渴望作为禁欲或减少药物使用的调解人。在建议的项目中，我们 计划检查渴望是兴奋剂使用障碍的结果，也是其他结果的中介。 更具体地说，在目标1中，我们将比较9种药物(在11个随机对照试验中)对兴奋剂药物渴求的影响。 在目标2中，我们将评估在试验过程中渴望的变化与其他结果的变化之间的联系，以及 渴望在治疗对这些结果的影响中的潜在中介作用。在目标3中，我们将探索 不同亚组中药物效果的差异以及渴望与其他结果的关系 病人的数量。我们建议使用在11项随机对照试验中的1,845名患者的个人参与者数据 NIDA的临床试验网络(CTN)和相关试验的背景，以实现这些研究目标。该项目 有可能对更好地理解渴求在持续发展中的作用做出重大贡献 兴奋剂使用障碍及药物对兴奋剂使用障碍的潜在影响 抗欲望的品质。具有抗渴求特性的药物目前用于治疗尼古丁和 酒精使用障碍并在治疗兴奋剂使用障碍方面显示出令人振奋的结果。该项目 也代表着有效地使用NIDA的RCT数据来回答在 原创研究。这些发现将有助于确定未来动力充足的试验的候选药物 基于候选药物的短期抗渴求效果，并对 正在努力寻找治疗兴奋剂使用障碍的有效药物治疗方法。