Evaluating a Mechanistically-Supported Pharmacotherapy to Treat Acute and Protracted Opioid Withdrawal

评估治疗急性和长期阿片类药物戒断的机械支持药物疗法

• 批准号: 10674929
• 负责人: Cecilia Bergeria
• 金额: $ 77.99万
• 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 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10674929
• 关键词: Ache; Acute; Address; Agonist; Ambulatory Care; Anxiety; Biochemical; Blood; Buprenorphine; Buspirone; Caring; Cells; Clinical; Data; Dopamine; Dopamine D2 Receptor; Dose; Double-Blind Method; Dropout; Economic Burden; Enrollment; Evaluation; FDA approved; Individual; Inpatients; Label; Marketing; Measurement; Measures; Methods; Molecular Conformation; Morphine; Muscle; Naltrexone; Opioid; Outpatients; Participant; Patients; Persons; Pharmaceutical Preparations; Pharmacotherapy; Phase; Pilot Projects; Placebo Control; Placebos; Publishing; Randomized; Relapse; Reporting; Research Design; Research Support; Residential Treatment; Risk Reduction; Rodent; Safety; Sampling; Serotonergic System; Serotonin; Serotonin Receptor 5-HT1A; Severities; Standardization; Stress; System; Treatment outcome; Urinalysis; Visit; Withdrawal; Withdrawal Symptom; antagonist; bone; conformational alteration; craving; depression model; desensitization; diaries; disorder risk; efficacy evaluation; improved; inpatient service; male; opioid epidemic; opioid tapering; opioid use; opioid use disorder; opioid withdrawal; pre-clinical; pre-clinical research; preclinical study; primary outcome; receptor; relapse prevention; relapse risk; treatment planning

There is substantial need to improve treatment for opioid use disorder (OUD). Buspirone is a mechanistically supported medication with robust preclinical and preliminary clinical support for treating opioid withdrawal and decreasing relapse. Buspirone has the utility to treat both acute and protracted withdrawal periods. We are experts in the measurement, evaluation and treatment of opioid withdrawal symptoms and have recently completed an RCT pilot study (n=16) which provides the initial safety, feasibility, and efficacy data to support a more thorough evaluation of buspirone to mitigate withdrawal when administered as an adjunct to a residential stepwise opioid taper. We propose a rigorous, Phase II, three-group, placebo-controlled double-blind RCT to evaluate the efficacy of buspirone for (1) acute withdrawal as an adjunctive pharmacotherapy to a residential opioid stepwise taper and (2) protracted withdrawal during an outpatient phase following taper completion. During the 12-day residential phase, 100 participants with OUD will be enrolled, stabilized on morphine, undergo a morphine stepwise taper, and complete a post-taper observation period where they will have the opportunity to initiate long-term buprenorphine or extended-release naltrexone. The outpatient phase will take place over the course of a 4-week period and will consist of weekly in-person visits and daily diary reports of their withdrawal and craving severity and anxiety. Individuals with OUD (n=100) will be randomized to one of three groups (1) buspirone during both residential and outpatient phases, (2) buspirone during the residential phase and placebo during the outpatient phase, and (3) placebo during both the residential and outpatient phases. We aim to complete 90 participants (30/group). We will collect measures of withdrawal, craving (acute and tonic), anxiety, medication acceptability, and biochemical measures of opioid use. Primary Aim 1 evaluates the impact of buspirone on acute and protracted withdrawal. We hypothesize participants who receive buspirone during both the residential and outpatient phases of the study will have the lowest overall opioid withdrawal severity. Primary Aim 2 evaluates the impact of buspirone on acute and tonic craving. We hypothesize participants that receive buspirone during both residential and outpatient phases will have the lowest tonic craving and that participants will show significantly lower acute craving when they are actively receiving buspirone. Primary Aim 3 evaluates whether retention and relapse prevention are impacted by buspirone. We hypothesize that buspirone used during a residential opioid taper will increase treatment retention and that buspirone used during the outpatient phase will decrease rates of relapse. Primary Aim 4 evaluates whether buspirone mitigates anxiety during residential and outpatient treatment for opioid use disorder. We hypothesize that buspirone will show modest reductions in anxiety during residential and outpatient treatment. This study will collect the data needed to determine whether buspirone is an effective method for improving treatment outcomes for OUD during acute and protracted opioid withdrawal periods.

有大量需要改进阿片类药物使用障碍(OUD)的治疗。丁螺环酮是一种机械上的 有强有力的临床前和初步临床支持的支持药物治疗阿片类药物戒断和 减少复发。丁螺环酮对急性戒断期和长期戒断期均有效。我们是 测量、评估和治疗阿片类药物戒断症状的专家最近 完成了随机对照试验试验研究(n=16)，该研究提供了初步的安全性、可行性和有效性数据，以支持 丁螺环酮作为住宅辅助用药时缓解戒断症状的更全面评估 逐步减少阿片类药物。我们提出了一个严格的，第二阶段，三组，安慰剂对照的双盲随机对照试验 丁螺环酮对1例住院患者急性戒断的疗效评价 阿片类药物逐步缩减和(2)在缩减完成后的门诊阶段长期戒断。 在为期12天的住院阶段，100名患有OUD的参与者将被登记，使用吗啡稳定下来， 接受吗啡逐步缩减，并完成缩减后的观察期，在那里他们将有 启动长期丁丙诺啡或缓释纳曲酮的机会。门诊阶段将需要 在为期4周的时间内，将包括每周面对面访问和每日日记报告 他们的退缩和渴望的严重性和焦虑感。患有OUD(n=100)的个体将被随机分配到以下一组 三组(1)住院期和门诊期丁螺环酮，(2)住院期丁螺环酮 门诊期间的阶段和安慰剂，以及(3)住院和门诊期间的安慰剂 阶段。我们的目标是完成90名参与者(30名/组)。我们将收集戒除、渴求的措施 (急性和补药)、焦虑、药物可接受性和阿片类药物使用的生化指标。主要目标1 评估丁螺环酮对急性和长期戒断的影响。我们假设参与者是 在住院和门诊阶段接受丁螺环酮治疗的总体效果最低 阿片类药物戒断的严重性。主要目的2评估丁螺环酮对急性和补充性渴望的影响。 我们假设在住院期间和门诊期间都接受丁螺环酮治疗的参与者将有 最低的补品渴望，当参与者积极时，他们的强烈渴望将显著降低 注射丁螺环酮。主要目标3评估保留和预防复发是否受到以下因素的影响 丁螺环酮。我们假设丁螺环酮在居民阿片类药物减量期间使用会增加治疗。 保留和在门诊阶段使用丁螺环酮将降低复发率。主要目标4 评估丁螺环酮是否缓解住院和门诊阿片类药物治疗期间的焦虑 使用无序。我们假设丁螺环酮在住院期间和住院期间会有适度的焦虑降低。 门诊治疗。这项研究将收集确定丁螺环酮是否有效所需的数据 改善急性和长期阿片类药物戒断期间OUD治疗结果的方法。