CNS Effects of Alcohol: Cellular Neurobiology

项目摘要 此请求是对我的AA006420临床部分--斯克里普斯研究中心--的行政补充 研究所的酒精研究中心(TSRI-ARC)，直接成本为140,000美元，以抵消损失和成本 由于新冠肺炎大流行而产生的。前几年的任何结转资金都已经花光了。影响 大流行对项目进展的影响：大流行导致我们的临床研究实验室关闭， 2020年3月中旬至2021年3月中旬暂停科目招募，使我们无法满足 Parent Grant的具体目标，即评估确定的前两个候选药物的治疗潜力 由TSRI-ARC的基础科学家使用我们经过验证的AUD人体实验室模型。剩余工时 项目：我们必须为研究中的每种药物招募50名受试者并将其随机化，以充分测试研究 假设，基于父母赠款中的权力分析，在赠款结束日期12/31/22之前。至 为了达到我们的具体目标，我们已经为这两项研究获得了药物供应、IND和IRB的批准 家长助学金规定：1.)选择性糖皮质激素受体(GR)拮抗剂CORT118335和2. Suvorexant，一种双重增食欲素1和2受体(OrxR)拮抗剂。大流行目前的财务影响 与补充要求相联系：大流行对我的ARC部分的财务影响主要是 2020年3月至2021年3月在实验室关闭期间支付给临床工作人员的工资损失93,400美元，而 无法注册科目。我们还损失了已支付的主题招聘广告费用3320美元 在关闭实验室之前，为工作人员和受试者支付了3163美元的个人防护装备，并发生了 需要将我们的Suvoxant研究的过夜部分从我们毗邻的斯克里普斯格林医院转移过来 由于他们无法容纳研究对象，鉴于他们是一家普通内科医院 以及优先安排新冠患者的人员和床位。我们成功地通过谈判使用了阿尔特曼 加州大学圣迭戈分校临床翻译研究所(ACTRI)提供过夜服务。这导致了以下情况 完成Suvorexant研究所需的50名受试者的额外Covid相关成本： UCSD特权医生的咨询费为12,500美元，陪护费为12,000美元，R/T为2,500美元 TSRI和UCSD之间50名受试者的交通费，以及UCSD调查药房费用13,117美元。 如果行政补充资金得不到奖励，对项目的影响：加在一起，每一个 两个项目很有可能通过翻译Basic来对该领域产生持续、强大的影响 AUD基于神经科学的新治疗策略的科学发现。重要的是，有工业 有兴趣将每个靶点向前推进，作为澳元的治疗方法。如果资金未获奖，则以 招聘目标无法实现，研究将动力不足，结果将不确定， 潜在的虚假负面结果，可能会挫伤对这些小说未来发展的热情 澳元的药物靶点。

Project Summary This request is for an administrative supplement to my clinical component of AA006420, The Scripps Research Institute's Alcohol Research Center (TSRI-ARC), for $140,000 in direct costs to offset the losses and costs incurred due to the COVID pandemic. Any carryover funds from previous years have been expended. Impact of the pandemic on project progress: The pandemic resulted in closure of our clinical research lab and suspension of subject recruitment from mid-March 2020 thru mid-March 2021, making us unable to meet our parent grant's specific aims, i.e., to evaluate the therapeutic potential of the top two drug candidates identified by TSRI-ARC's basic scientists, using our validated human laboratory model of AUD. Work remaining on project: We must recruit and randomize 50 subjects for each drug under study to adequately test study hypotheses, based on power analyses in the parent grant, prior to the end date of the grant on 12/31/22. To meet our specific aims, we have secured drug supply, INDs, and IRB approvals for the two studies as stipulated in the parent grant: 1.) CORT118335, a selective glucocorticoid receptor (GR) antagonist, and 2.) suvorexant, a dual orexin 1 and 2 receptor (OrxR) antagonist. Financial impact of the pandemic as it is linked to the supplement request: The financial impact of the pandemic on my ARC component is primarily the loss of $93,400 in salaries paid to clinical staff during lab closure from March 2020 to March 2021 while unable to enroll subjects. We also lost advertising costs of $3,320 for subject recruitment that had been paid going into lab closure, $3,163 paid for personal protective equipment (PPE) for staff and subjects, and incurred the need to transfer the overnight portion of our suvorexant study from our adjoining Scripps Green Hospital due to their inability to accommodate research subjects, given their status as a general medical hospital and the prioritization of personnel and beds for COVID patients. We successfully negotiated to use the Altman Clinical Translational Research Institute (ACTRI) at UCSD for the overnight stay. This incurred the following additional covid-related costs of completing the required enrollment of 50 subjects for the suvorexant study: $12,500 consulting fees for physician with UCSD privileges, $12,000 chaperone fees, $2,500 R/T transportation for 50 subjects between TSRI and UCSD, and $13,117 UCSD investigational pharmacy fees. Impact on the project if administrative supplement funds are not awarded: Taken together, each of these two projects has a high likelihood of exerting a sustained, powerful influence on the field by translating basic science findings into novel neuroscience-based therapeutic strategies for AUD. Importantly, there is industry interest in moving each target forward as a treatment for AUD. If the funds are not awarded, subject recruitment goals cannot be met, studies will be under-powered, and results will be inconclusive, with potentially false negative outcomes that are likely to dampen enthusiasm for future development of these novel drug targets for AUD.