This study is part of the NIH’s Helping to End Addiction Long-term (HEAL) initiative to speed scientific solutions to the national opioid public health crisis. The NIH HEAL Initiative bolsters research across NIH to improve treatment for opioid misuse and addiction. The Appalachian Node of NIDA Clinical Trials Network (CTN) is committed to discovering novel strategies, new interventions and conducting clinical trials to improve real-world outcomes for individuals who use drugs and have substance use disorders (SUDs) in central Appalachia and the mid-Atlantic region. Our Node has been a collaboration between the University of Pittsburgh (Pitt) [mPI: Liebschutz, Winstanley], West Virginia University (WVU) and Penn State College of Medicine (PSU); and our Node will be expanded to include the University of Maryland, Baltimore (UMB) and the PCORI-funded PaTH research network that includes harmonized electronic health records (EHR) from nine academic health systems. The expansion of Node to include UMB and the PaTH network will allow us to reach minoritized underserved urban communities like Baltimore, Philadelphia, Detroit and Chicago. Our region has had among the highest rate of overdose deaths for decades, and our expanded Node will be uniquely situated to compare intervention effectiveness across geographic regions (urban/rural/Appalachian), diverse patients (race/ethnicity) and under-served populations. During our first five years as a CTN node, we have led six CTN studies and we have participated in eight trials, often as one of the highest recruiting sites in the country. Collectively, we have published 52 CTN-related manuscripts, with 8 additional in revision or submitted and our node members have facilitated 223 training events that have reached >11,000 individuals. The aims of the Node are to: 1) conduct community-informed multisite trials that seek to improve outcomes for patients with SUDs with an emphasis on minoritized, rural and under-served communities; 2) propose clinical studies to test novel adjunctive therapeutics for individuals with methamphetamine use disorder (focused ultrasound; Lead: Mahoney), investigate the effectiveness of glucagon-like peptide 1 (GLP-1) to treat cocaine use disorder (Leads: Kattakuzhy & Kawasaki), investigate strategies to manage emergent medical complications of novel psychoactive substance (xylazine, Lead: Jawa) and reduce stigma associated with medications for opioid use disorder (Lead: Hamm); 3) expand our reach through collaboration with the PaTH network to facilitate data harmonization and secondary data analysis of emerging clinical needs; 4) train students, health professionals and related community service providers in clinical research and state-of-the art interventions to improve outcomes among individuals using drugs and 5) disseminate scientific findings to key stakeholders and communities, develop toolkits to facilitate rapid uptake of novel strategies into routine clinical practice and utilize human-centered design activities with our Community Advisory Board (CAB) and other community members. Our CAB meets quarterly and is involved across all phases of CTN study development, execution and dissemination. Our CAB includes representatives of people with lived experience of SUDs, policy makers, payers, clinicians and health care administration.

Narrative The epidemic of opioid and stimulant overdose deaths and associated morbidity have decreased life expectancy and devastated communities. The Appalachian Node of the NIDA Clinical Trials Network, a collaboration between Penn State University, University of Maryland, University of Pittsburgh, West Virginia University, and the PaTH network, will test novel solutions to ameliorate the epidemic by harnessing local resources, employing health technology, and incorporating bioinformatics.