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: 10462826
• 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/10462826
• 关键词: Abstinence; American; Baclofen; Behavioral; Bupropion; Characteristics; Chronic; Clinical; Clinical Treatment; Clinical Trials Network; Cocaine; Combination Medication; Complex; Data; Dependence; Distress; Dropout; Drug usage; Effectiveness; Epidemic; Equilibrium; Ethnic Origin; Evaluation; FDA approved; Frequencies; Future; Health; Heterogeneity; Individual; Measures; Mediating; Mediator of activation protein; Methamphetamine use disorder; Modafinil; Naltrexone; National Institute of Drug Abuse; Ondansetron; Opioid; Outcome; Overdose; Participant; Patients; Pattern; Persons; Pharmaceutical Preparations; Pharmacological Treatment; Phase; Property; Publications; Race; Randomized Controlled Trials; 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; Weight; Withdrawal; Withdrawal Symptom; alcohol abuse therapy; alcohol craving; alcohol use disorder; analytical method; base; cabergoline; clinically relevant; cocaine use; comorbidity; craving; data harmonization; depressive symptoms; drug craving; drug relapse; drug seeking behavior; experience; follow-up; methamphetamine use; morphogens; nicotine craving; nicotine treatment; nicotine use; novel; patient subsets; 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 包括可卡因和甲基苯丙胺使用障碍在内的兴奋剂使用障碍影响着数百万人的生活， 美国人，并与重大的健康和社会后果。目前没有FDA- 批准用于治疗兴奋剂使用障碍的药物。大多数随机对照试验（RCT） 寻找有效药物的时间短，通常持续8-12周，样本量小 尺寸.达到持久的戒除兴奋剂可能需要更长的治疗和检测这些影响 可能需要更大的样本。然而，现有的试验可以提供关于短期结果的信息， 比禁欲更早实现且不那么严格的治疗，因此有助于确定候选者 为未来的长期和更大规模的试验提供药物。药物渴望可能是最有希望的这种短期- 长期成果。兴奋剂使用障碍的特征是大量使用兴奋剂，然后是短暂的 有戒断症状的禁欲。这些症状会持续几天，然后增加药物剂量。 经常导致复发的渴望。对药物的渴望是这些药物循环的中心现象 使用.然而，很少有研究专门关注渴望作为兴奋剂使用障碍的结果 或减少对毒品的渴望作为戒断或减少毒品使用的媒介。在项目中，我们 计划检查渴望作为兴奋剂使用障碍的结果以及其他结果的中介。 更具体地说，在目标1中，我们将比较9种药物（11项RCT）对刺激性药物渴望的影响。 在目标2中，我们将评估试验期间渴望变化与其他结果变化的关联， 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 药物效果的变化以及渴望与亚组中其他结果的关联 病人。我们建议使用来自11项随机对照试验中1，845例患者的个体参与者数据， NIDA的临床试验网络（CTN）和相关试验的背景下，以实现这些研究目标。项目 有可能大大有助于更好地理解渴望在持续的 兴奋剂使用障碍和药物对兴奋剂使用障碍的潜在影响， 反渴望的品质具有抗渴望特性的药物目前用于治疗尼古丁， 酒精使用障碍，并在治疗兴奋剂使用障碍方面显示出有希望的结果。项目 也代表了NIDA的随机对照试验数据的有效利用，以回答在 原创研究这些发现将有助于为未来的充分试验确定候选药物 基于候选药物的短期抗渴望作用，并显著有助于 目前正在努力寻找有效的药物治疗兴奋剂使用障碍。