Funded Projects

Access to harm reduction services are often limited in rural areas. Secondary distribution is a potentially promising strategy for rural areas that involves people sharing harm reduction supplies such as naloxone or fentanyl test strips with other people who use drugs that do not come into contact with harm reduction service providers. This project aims to examine drug use and use of harm reduction services among people in rural communities, as well as highlight factors that make people more or less likely to use secondary distribution approaches.

Opioid use disorder (OUD) is a significant public health problem in the United States. Particularly troubling is the rapid evolution of an opioid epidemic within the past decade, characterized by a surge in unintentional overdose deaths involving synthetic opioids, such as fentanyl. The current standard of care for opioid overdose is reversal with opioid antagonist naloxone. Naloxone is effective at reversing overdose from prescription opioids and heroin, but less effective when combating fentanyl, due to fentanyl?s high potency. Therapeutic monoclonal antibodies (mAbs) against fentanyl could overcome this problem by specifically preventing the drug from entering the central nervous system, averting overdose and attenuating opioid-induced respiratory depression. This study will develop and design of laboratory protocols needed to establish a Good Manufacturing Practice (GMP) process, quality assurance protocol, and stability profile for a new human mAb against fentanyl. Subsequent production of current GMP material will enable Good Laboratory Practice (GLP) toxicology studies in rats and dogs and eventually a Phase I/IIa clinical trial. This material will also be used in final opioid-induced respiratory depression studies in mice and non-human primates to confirm therapeutic efficacy of final drug product. If successful, these activities will enable filing for an investigational new drug application for this mAb candidate with the FDA.

Effective treatment for OUD has been shown to improve patient outcomes and reduce health care costs; however, evidence of this effect in primary care settings is severely limited. The health economic findings from this study will supplement the parent PROUD trial’s results regarding clinical effectiveness and implementation outcomes and provide critical contextual information for health systems and other health care stakeholders. The study will evaluate the economic viability of the PROUD collaborative care model for OUD—that is, from the perspective of the health care sector, to what extent do the downstream cost savings associated with improved patient outcomes offset the additional costs of the PROUD intervention? The specific aims are to (1) estimate the start-up and ongoing management costs of the PROUD intervention, (2) assess costs associated with health care utilization for patients who receive primary care treatment in PROUD and usual care clinics and have been identified with recognized OUDs before clinic randomization, and (3) estimate the economic value of the PROUD intervention, measured as net monetary benefit (NMB, incremental benefit minus incremental cost), from the health care sector perspective.

Effective treatment for OUD has been shown to improve patient outcomes and reduce health care costs; however, evidence of this effect in primary care settings is severely limited. The health economic findings from this study will supplement the parent PROUD trial’s results regarding clinical effectiveness and implementation outcomes and provide critical contextual information for health systems and other health care stakeholders. The study will evaluate the economic viability of the PROUD collaborative care model for OUD—that is, from the perspective of the health care sector, to what extent do the downstream cost savings associated with improved patient outcomes offset the additional costs of the PROUD intervention? The specific aims are to (1) estimate the start-up and ongoing management costs of the PROUD intervention, (2) assess costs associated with health care utilization for patients who receive primary care treatment in PROUD and usual care clinics and have been identified with recognized OUDs before clinic randomization, and (3) estimate the economic value of the PROUD intervention, measured as net monetary benefit (NMB, incremental benefit minus incremental cost), from the health care sector perspective.

While the mu opioid receptor (MOR) antagonist naloxone has proven invaluable as an opioid overdose antidote, naloxone suffers from a very short duration of action (half-life is approximately 1 hour) and has been found to be less effective against newer, long-acting opioids, including fentanyl (half-life is approximately 7–10 hours). This leads to a highly lethal and increasingly prevalent phenomenon known as “renarcotization,” wherein an overdose patient revived with naloxone can re-enter an overdose state from residual fentanyl in the body. Thus, there is a critical need to develop a long-acting MOR antagonist formulation that can address renarcotization by providing multi-hour protection. The goal of this project is to reformulate naloxone using FDA-approved microencapsulation technology into a long-acting injectable (LAI) that can provide 12–24 hours of sustained antagonist activity in vivo. It will employ a proprietary Computational Drug Delivery™ software, called ADSR™, to perform in silico formulation optimization as well as to predict its in vitro dissolution and in vivo pharmacokinetic behavior.

Quality implementation of evidence-based programs (EBPs) in community settings for youth is critical for reducing the burden of alcohol, tobacco and other drug (ATOD) use and its consequences. EBPs delivered in schools are an efficient way to reach large populations of young people, including those underserved by other settings, and reduce and prevent ATOD use. Yet youth rarely receive EBPs as intended in community settings, including schools. This training and research plan will prepare the investigator to become an independent scholar in the implementation of theories and frameworks to better understand factors related to program delivery—approaches to enhancing ATOD programs for youth in community settings. More specifically, the training will allow him to expand the application of Consolidated Framework for Implementation Research (CFIR) to inform approaches to enhancing effective EBP delivery. The proposed training and research plan extends current implementation research to focus applying implementation theories, frameworks and strategies in other community settings (schools) and on economic evaluation of implementation strategies. The results are expected to improve current efforts to deliver EBPs in diverse community settings and aid in applying evidence-based implementation strategies in the school context to ultimately reduce and prevent ATOD use among youth.

Many states across the country have experienced an increase in children involved in the foster care system because of young parental opioid and methamphetamine use disorders (OUD; MUD). The Families Actively Improving Relationships (FAIR) program is a recently developed, rigorously evaluated, intensive outpatient treatment program for parents involved in the child welfare system for parental OUD and/or MUD. The FAIR effectiveness trial showed the potential for FAIR to be adapted as a prevention program, and to be implemented in counties with low service availability and access. This project will adapt and implement FAIR for prevention in collaboration with Oregon State Department of Human Services (DHS). Across two counties, parents referred by DHS for OUD or MUD with risk for escalation will be recruited and randomized to receive the adapted FAIR as prevention, or standard case management and referral. Outcomes will inform further FAIR refinement and potential broader scale-up.

This project seeks to develop and test a “train-the-trainer” curriculum and training experience that will facilitate the spread and use of the 6BBs by adapting the 6BBs framework and toolkit for health systems and other organizations, training personnel to facilitate its implementation and monitoring results of this implementation.

Little is known about what motivates people to use multiple drugs. Understanding these factors is important for tailoring treatment services. Behavioral economic theory, which determines how much value individuals assign to drugs and potential negative consequences, provides a framework to understand the choices people make. This project will identify patterns, motivating factors, and long-term trajectories of opioid-involved polysubstance use behaviors and treatment. This research will use a range of methods to analyze substance use episodes as well as examine motives and preferences associated with polysubstance use behaviors and how they change over time. The findings will be combined into a toolkit to inform timing, type, and tailoring of interventions and policies to guide implementation of effective clinical strategies and policies for managing polysubstance use in healthcare systems.

The International Classification of Diseases 10th revision codes are insufficient to accurately identify individuals who use opioids and stimulants together. This project will search already collected electronic health record data using a computer program to identify people with polysubstance use and determine what health care they receive. The research will improve understanding of polysubstance use in a region of Los Angeles, California, with very high rates of overdoses involving fentanyl and stimulants. 

Osteoarthritis is a degenerative joint disease marked by progressively worsening chronic joint pain that affects function and quality of life. Non-opioid, alternative medications are needed for people with this condition. Joint inflammation, damage, and pain involve signaling through the interleukin-6/glycoprotein 130 pathway. This project will test blocking this pathway in rodents with a new molecule with improved drug-like properties, toward developing an oral medication for osteoarthritis.