CNS Effects of Alcohol: Cellular Neurobiology

酒精对中枢神经系统的影响：细胞神经生物学

• 批准号: 10834659
• 负责人: BARBARA J MASON
• 金额: $ 10万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-20 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10834659
• 关键词: Abstinence; Address; Administrative Supplement; Animal Model; Award; Back; Basic Science; Budgets; Cellular Neurobiology; Clinical; Clinical Data; Collaborations; Communities; Data; Data Analyses; Direct Costs; Enrollment; Facilities and Administrative Costs; Funding; Goals; Grant; Heavy Drinking; Human; Impairment; Individual; Industry; Inpatients; Institution; Laboratories; Measures; Mediating; Modification; Neurobiology; Neuropharmacology; Neurosciences; Phase; Progress Reports; Publications; Relapse; Research; Research Institute; Role; Sample Size; Sampling Studies; Therapeutic; Translating; Translations; alcohol abuse therapy; alcohol effect; alcohol research; alcohol use disorder; antagonist; biological adaptation to stress; data management; drinking; hypocretin; interest; neurobiological mechanism; novel; pre-clinical; translational goal

Project Summary This request is for an administrative supplement to the Administrative Core of AA006420, The Scripps Research Institute’s Alcohol Research Center (TSRI-ARC), for $55,238 in direct costs. The purpose of this supplement request is to support data management, analysis, interpretation, and publication of results from the first completed hypocretin (orexin) antagonist study in humans with alcohol use disorder (AUD). Enrollment for this Phase 2a study was completed in Year 39 of the TSRI-ARC to meet a Specific Aim of the Clinical Component. Covid-related overnight staffing shortages for the inpatient component of the study at a collaborating institution necessitated extending subject enrollment through November 2022 to optimize study sample size by the end date of the grant on 12/31/22. The extended enrollment period only permitted cursory data entry, management, and analysis of top-line results to complete the final progress report for the grant and the posting of topline results on clinicaltrials.gov. Comprehensive analysis of results is critical for determining the direction of the pre-clinical hypocretin antagonist studies, including what parameters to measure in Year 40 of the TSRI-ARC Neuropharmacology Research Component, which has a primary focus on studying hypocretin in animal models of AUD. Funding for the clinical analyses was not included in the renewal application because there was no way to anticipate that the above circumstances would necessitate extending the enrollment period and preclude completion of data analysis within the proposed timeframe. Furthermore, we elected to sunset the Clinical Component in the renewal and any carryover funds from previous years have been expended, the Center budget was cut by 10%, and our indirect cost rate increased by 4% since the renewal was submitted. Thus, it is not possible to re-budget funds in the renewal to support the suvorexant human laboratory data analyses without significantly negatively impacting the Specific Aims of the renewal projects. However, part of Dr. Mason’s role as Director of the Administrative Core in Year 40 of the renewal is to facilitate the translation of basic research, including back translation from human studies, and these clinical data are critical to this aim. We understand it is unusual to request an administrative supplement in the first year of a funding cycle, but it is counterproductive to wait a year while the Neuropharmacology Component implements a research plan that may require modification based on information collected in the hypocretin antagonist clinical proof-of-concept study. This project has a high likelihood of exerting a sustained, powerful influence on the field by translating basic science findings into a novel neuroscience-based therapeutic strategy for AUD. Importantly, there is industry interest in moving this target forward as a treatment for AUD. If the requested funds are awarded, such translational goals can be met, and planned information will be available to guide the Neuropharmacology Component and the alcohol research community.

项目摘要 本申请是对AA 006420管理核心的管理补充，斯克里普斯 研究所的酒精研究中心（TSRI-ARC），直接费用为55,238美元。这样做的目的 补充请求是为了支持数据管理、分析、解释和结果发布， 首次完成了对酒精使用障碍（AUD）患者的下丘脑泌素（食欲素）拮抗剂研究。招生 这项2a期研究在TSRI-ARC的第39年完成，以满足临床研究的特定目标。 成分研究住院部分的Covid相关过夜人员短缺， 合作机构需要将受试者入组时间延长至2022年11月，以优化研究 在2022年12月31日补助金结束日期之前的样本量。延长的注册期只允许粗略地 数据输入、管理和分析顶级结果，以完成赠款的最终进度报告， 在clinicaltrials.gov上发布顶线结果。对结果的全面分析对于确定 下丘脑泌素拮抗剂临床前研究的方向，包括在40年测量哪些参数 TSRI-ARC神经药理学研究部分，其主要重点是研究 下丘脑泌素在AUD动物模型中的作用。临床分析的资金不包括在更新中 申请，因为没有办法预料到上述情况将需要延长 入组期，并排除在拟定时间范围内完成数据分析。此外，委员会认为， 我们选择在更新中终止临床部分，并且前几年的任何结转资金都已 自2000年以来，中心的预算削减了10%，我们的间接成本率增加了4%。 更新已提交。因此，不可能在更新中重新预算资金以支持苏沃雷生 人类实验室数据分析，不会对更新的具体目的产生显著负面影响 项目然而，梅森博士在续约40年期间担任行政核心主任的部分职责是 促进基础研究的翻译，包括人类研究的翻译，以及这些临床研究的翻译。 数据对于实现这一目标至关重要。我们理解，在第一次会议上要求行政补充是不寻常的。 一年的资金周期，但它是适得其反，等待一年，而神经药理学组件 根据下丘脑泌素中收集的信息实施可能需要修改的研究计划 拮抗剂临床概念验证研究。这个项目有很高的可能性发挥持续的，强大的 通过将基础科学发现转化为新的基于神经科学的治疗方法， 澳元策略重要的是，业界有兴趣将这一目标作为澳元的治疗方法。如果 所要求的资金被授予，这样的翻译目标可以实现，计划的信息将 可用于指导神经药理学组件和酒精研究社区。