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

基本信息

批准号：
10419301
负责人：
BARBARA J MASON
金额：
$ 24.85万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-10 至 2021-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10419301
关键词：
Abstinence Administrative Supplement Advertising Aftercare Alcohols Animal Model Animals Anxiety Attenuated Basic Science Beds Biochemistry Biological Markers Blood COVID-19 pandemic COVID-19 patient Cellular Neurobiology Clinical Clinical Research Collaborations Consult Controlled Clinical Trials DSM-V Development Direct Costs Dose Double-Blind Method Drug Antagonism Drug Kinetics Electrocardiogram Electrophysiology (science)Enrollment Executive Dysfunction FDA approved Fees Female Funding Future Glucocorticoid Receptor Glutamates Goals Grant Homeostasis Hospitals Human Human Resources Individual Industry Institutional Review Boards Intoxication Investigation Laboratories Lead Link Measures Mediation Medical Methods Microtubules Mifepristone Modeling Molecular Chaperones Naltrexone National Institute on Alcohol Abuse and Alcoholism Neuroimmune Neurosciences Outcome Parents Performance Peripheral Pharmaceutical Fees Pharmaceutical Preparations Phase Physicians Placebos Plasma Progesterone Progesterone Receptors Randomized Randomized Controlled Trials Research Institute Research Personnel Research Priority Research Project Grants Research Subjects Risk Safety Scientist Secure Serotonin Severities Sleep Sleeplessness Standardization Stress Study models Suspensions System Testing Therapeutic Therapeutic Uses Translating Translational Research Transportation Urine Validation Wages Withdrawal Work abortion acamprosate addiction alcohol cue alcohol effect alcohol research alcohol use disorder base coronavirus disease cost craving depression model design disorder later incidence prevention drinking drug candidate duloxetine efficacy evaluation executive function follow-up gabapentin glucocorticoid receptor alpha human data human study hypocretin hypothalamic-pituitary-adrenal axis in vivo interdisciplinary approach interest male meetings negative affect new therapeutic target next generation novel novel therapeutic intervention novel therapeutics pandemic disease parent grant personal protective equipment potential biomarker power analysis pre-clinical pregabalin primary endpoint receptor recruit response response biomarker side effect volunteer

项目摘要

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.

项目概要此请求是对我的 AA006420（斯克里普斯研究）临床部分的行政补充研究所酒精研究中心 (TSRI-ARC)，直接费用 140,000 美元，以抵消损失和成本因新冠肺炎疫情而发生。往年结转的资金均已支出。影响疫情对项目进展的影响：疫情导致我们的临床研究实验室关闭，从2020年3月中旬到2021年3月中旬暂停受试者招募，使我们无法满足我们的要求家长资助的具体目标，即评估已确定的前两种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 人体实验室模型进行研究。剩余工作项目：我们必须为每种正在研究的药物招募并随机分配 50 名受试者，以充分测试研究在 2022 年 12 月 31 日补助金结束日期之前，根据母补助金中的功效分析做出假设。到为了满足我们的具体目标，我们已经为这两项研究获得了药物供应、IND 和 IRB 批准：母基金中规定：1.) CORT118335，一种选择性糖皮质激素受体 (GR) 拮抗剂，以及 2.) suvorexant，一种双重食欲素 1 和 2 受体 (OrxR) 拮抗剂。大流行的财务影响与补充请求相关：疫情对我的 ARC 部分的财务影响主要是 2020 年 3 月至 2021 年 3 月实验室关闭期间支付给临床人员的工资损失 93,400 美元无法注册科目。我们还损失了 3,320 美元的受试者招募广告费用实验室关闭，为工作人员和受试者支付了 3,163 美元的个人防护装备 (PPE)，并产生了需要从毗邻的斯克里普斯格林医院转移我们的 suvorexant 研究的过夜部分由于其作为综合医院的地位，无法容纳研究对象以及为新冠肺炎患者提供人员和床位的优先顺序。我们成功协商使用奥特曼 UCSD 临床转化研究所 (ACTRI) 过夜。这导致了以下情况完成 suvorexant 研究所需的 50 名受试者注册所需的额外 covid 相关费用：具有 UCSD 特权的医生咨询费为 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 13,117 美元的 UCSD 研究药房费。如果不授予行政补助资金对项目的影响：综合起来，每一项两个项目极有可能通过翻译基础知识对该领域产生持续、强大的影响基于神经科学的新型 AUD 治疗策略的科学发现。重要的是有产业有兴趣推动每个目标作为 AUD 的治疗方法。如果未获得资金，则招募目标无法实现，研究动力不足，结果不确定，潜在的虚假负面结果可能会削弱人们对这些小说未来发展的热情澳元的药物靶标。