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.

项目摘要该请求是为我在AA006420的临床组成部分的管理补充，Scripps Research 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共同大流行而产生的。往年的任何结转资金都已被花费。影响大流行在项目进步方面：大流行导致我们的临床研究实验室关闭从2020年3月中旬到3月中旬的2021年3月中旬的暂停招募，使我们无法满足我们的父母赠款的具体目的，即评估确定的前两个候选药物的治疗潜力由TSRI-ARC的基本科学家使用我们经过验证的人类实验室模型。继续进行工作项目：我们必须为每种正在研究的药物招募和随机分配50名受试者才能进行充分的测试研究基于父母赠款的权力分析的假设，在赠款的结束日期为12/31/22之前。到达到我们的具体目标，我们已确保两项研究的药物供应，IND和IRB批准为在父授予中规定：1。）Cort118335，选择性糖皮质激素受体（GR）拮抗剂和2.） Suvorexant，双双球蛋白1和2受体（ORXR）拮抗剂。大流行的财务影响与补充请求有关：大流行对我的ARC组件的财务影响主要是从2020年3月至2021年3月，在实验室关闭期间，损失了93,400美元的薪水支付给临床人员无法注册受试者。我们还损失了已支付的主题招聘的广告费用3,320美元进入实验室关闭，为员工和受试者支付了3,163美元的个人防护设备（PPE），并发生了需要从毗邻的Scripps绿色医院转移我们的Suvorexant研究的通宵部分由于他们无法容纳研究对象，因此他们作为一般医疗医院的地位以及共同患者的人员和床的优先级。我们成功地谈判了使用Altman UCSD的临床翻译研究所（ACTRI），用于过夜。这产生了以下完成suvorxant研究的50名受试者所需的50名受试者所需入学的其他成本：带UCSD特权的医师咨询费$ 12,500，$ 12,000陪伴费，$ 2,500 R/T TSRI和UCSD之间的50名受试者的运输，以及13,117美元的UCSD研究药房费用。如果未授予行政补充资金，则对项目的影响：共同两个项目很有可能通过翻译基本来对该领域产生持续，强大的影响科学发现是基于神经科学的新型AUD治疗策略。重要的是，有行业有兴趣将每个目标推向AUD的治疗方法。如果未授予资金，则无法实现招聘目标，研究将不足，结果将是尚无定论的潜在的虚假负面结果可能会抑制这些小说的未来发展的热情 AUD的药物目标。