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: 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
• 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

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 本申请是对我的AA 006420（Scripps研究）临床部分的行政补充 该研究所的酒精研究中心（TSRI-ARC），为140，000美元的直接成本，以抵消损失和成本 由于COVID大流行而产生。以往年度的任何结转资金都已支出。影响 疫情对项目进展的影响：疫情导致我们关闭了临床研究实验室， 从2020年3月中旬至2021年3月中旬暂停受试者招募，使我们无法满足我们的 父母补助金的具体目标，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，使用我们验证的AUD人体实验室模型。剩余工作 项目：我们必须为每种研究药物招募并随机分配50例受试者，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进行假设。到 为了实现我们的具体目标，我们已经为这两项研究获得了药物供应、IND和IRB批准， 在父母补助金中规定：1.）选择性糖皮质激素受体（GR）拮抗剂CORT 118335，和2.） suvorexant，一种双重食欲素1和2受体（OrxR）拮抗剂。大流行病目前的财务影响 与补充请求相关：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，同时 无法招募受试者。我们还损失了3，320美元的广告费用，用于已支付的受试者招募 进入实验室关闭，为工作人员和受试者支付了3，163美元的个人防护设备（PPE）， 需要将我们的suvorexant研究的过夜部分从我们毗邻的Scripps绿色医院转移 由于它们作为综合性医疗医院的地位， 以及新冠肺炎患者的人员和床位的优先顺序。我们成功地协商使用奥特曼 临床转化研究所（ACTRI）在UCSD过夜。这导致了以下情况 完成suvorexant研究所需的50例受试者入组的额外Covid相关费用： $12，500咨询费为医生与UCSD特权，$12，000陪护费，$2，500 R/T 50名受试者在TSRI和UCSD之间的交通费，以及13，117美元的UCSD研究药房费。 如果不提供行政补充资金，对项目的影响： 这两个项目很有可能通过翻译基础知识， 将科学发现转化为基于神经科学的新型AUD治疗策略。重要的是， 有兴趣将每个目标向前移动作为AUD的治疗。如果资金不到位， 招募目标无法实现，研究将动力不足，结果将是不确定的， 潜在的假阴性结果，可能会抑制这些小说未来发展的热情， 药物靶向AUD。