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.

Project Narrative Our collaboration with the multi-disciplinary approaches offered by TSRI-ARC investigators will open a path to identifying new medications for alcohol use disorder based on novel stress targets. These targets will be screened for safety and efficacy across the three stages of the addiction cycle in our human lab model, and peripheral measures of stress and drug concentration will be evaluated as potential biomarkers of response. Data from the human studies will provide clinical validation of targets identified by TSRI-ARC investigators and information about biomarkers of drug effects that may guide future studies across TSRI-ARC components.