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.

项目概要 此请求是对 AA006420 斯克里普斯行政核心的行政补充 研究所酒精研究中心 (TSRI-ARC)，直接成本为 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、解释和发布结果 第一个在患有酒精使用障碍 (AUD) 的人类中完成的下丘脑分泌素（食欲素）拮抗剂研究。报名参加 这项 2a 期研究于 TSRI-ARC 第 39 年完成，旨在满足临床的特定目标 成分。该研究的住院部分与新冠病毒相关的过夜人员短缺 合作机构需要将科目招生期限延长至 2022 年 11 月，以优化学习 截至赠款结束日期（2022 年 12 月 31 日）的样本量。延长招生期限只允许粗略 数据输入、管理和分析主要结果，以完成拨款的最终进度报告 在 ClinicalTrials.gov 上发布主要结果。结果的综合分析对于确定 临床前下丘脑分泌素拮抗剂研究的方向，包括 40 年要测量的参数 TSRI-ARC 神经药理学研究部分的主要重点是研究 AUD 动物模型中的下丘脑分泌素。临床分析的资助不包括在续约中 申请，因为无法预见上述情况需要延期 登记期并阻止在建议的时间范围内完成数据分析。此外， 我们选择在续约中取消临床部分，并且前几年的任何结转资金都已 支出增加后，中心预算削减了 10%，间接成本率自 2017 年以来增加了 4%。 续订已提交。因此，不可能在续约中重新制定预算资金来支持 suvorexant 人体实验室数据分析不会对更新的具体目标产生重大负面影响 项目。然而，梅森博士在续约第 40 年担任行政核心主任的部分职责是 促进基础研究的翻译，包括人类研究的回译，以及这些临床研究 数据对于实现这一目标至关重要。我们知道，第一次请求行政补充是不寻常的。 一个资助周期的一年，但等待一年而神经药理学部分会适得其反 实施一项可能需要根据下丘脑分泌素收集的信息进行修改的研究计划 拮抗剂临床概念验证研究。该项目很有可能发挥持续、强大的作用 通过将基础科学发现转化为基于神经科学的新型治疗方法对该领域产生影响 澳元策略。重要的是，业界有兴趣推动这一目标作为澳元的治疗方法。如果 所请求的资金已获得，此类转化目标可以实现，并且计划的信息将得到 可用于指导神经药理学部分和酒精研究界。