Funded Projects

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.

Non-punishment, support-based preventive interventions in schools are needed to reduce misuse of opioids and other substances among youth. This project will test an intervention to improve school climate by introducing a learning approach that encourages behavior that is supportive and respectful in middle schools. ISLA reduces the use of exclusionary and discipline practices, such as suspensions and expulsions, that can be racially discriminating. The research aims to improve inclusive teaching practices, student engagement, student-teacher relationships, and school climate, while reducing student misuse of opioids and other substances.

Juvenile justice (JJ)-involved youth represent a particularly vulnerable population for substance use and substance use disorders (SUDs), because they often experience mental health disorders, dysfunctional family/social relationships, and complex trauma. This study will adapt and test an intervention for preventing initiation and/or escalation of opioid misuse among older JJ-involved youth aging out of JJ (16-18 years), who are transitioning to their communities after a period of detainment in a secure treatment or correctional facility. Trust-Based Relational Intervention® (TBRI®, a relational, attachment-based intervention that promotes emotional regulation through interaction with responsive adults) will be adapted as a prevention intervention targeting youth at risk for substance use, especially non-medical use of opioids. Safe adults (e.g., parent/guardian) will be trained in behavior management techniques for empowering youth to appropriately express their needs, connecting them with others in pro-social ways, and correcting or reshaping undesirable behavior.

This project aims to develop a novel abuse deterrent formulation (ADF) that will be uniquely designed to prevent abuse of the prescription pill. The study will focus on the development of the ADF with design aspects specifically focused on abuse through insufflation, smoking, injection, and taking multiple pills. The study will also validate the design by putting the pill through a rigorous test following the procedures outlined by the FDA Abuse-Deterrent-Opioids-Evaluation and Labeling guidelines. The study could result in the development of a novel ADF that will be resistant to a wide range of tampering, resulting in a safer formulation and pill design.

Chronic pancreatitis is a painful condition often caused by long-term alcohol use, and patients often require treatment with strong pain medications, including opioids. Therefore, alternative treatments for chronic pancreatitis are needed. This project will use machine learning approaches to create a prediction tool based on electroencephalography analyses, sensory tests, and psychological questionnaires that can help determine which patients with chronic pancreatitis will benefit most from a specific type of treatment called endoscopic therapy.

Opioid use during pregnancy is associated with significant harmful health outcomes for infants including preterm birth, neonatal opioid withdrawal syndrome (NOWS), and impaired brain-related problems. Not all infants exposed to opioids develop NOWS, and there is a need for better diagnostic tests. This project will study specialized cell structures called vesicles that are released from the placenta, fetal brain, and central nervous system to communicate information about health of the fetus and placenta. This research on vesicles will be combined with data about NOWS diagnosis up to 1 month after birth. The research aims to generate molecular indicators (biomarkers) that predict which newborns develop NOWS, toward guiding safe and effective treatment for these newborns.

Effective overdose prevention requires timely, location-specific data to efficiently direct resources and interventions as well as to inform healthcare policy. However, rarely is such information available, resulting in responses that are frequently too late. This project will partner with local government agencies from Los Angeles County, California, to rapidly acquire and analyze information in near real-time from multiple sources to identify overdose hotspots and determine overdose metrics. This information will be used to develop a publicly available Rapid Overdose Surveillance Los Angeles online dashboard with built-in analytics. The dashboard will help determine the scope and specifics of overdose and opioid use in Los Angeles County to help target response and guide mobile addiction treatment and harm reduction services.

Substance use disorder (SUD) is a serious public health and socioeconomic burden. In this project, researchers will develop novel drug compounds that dually target orexin receptors and kappa opioid receptors, which have both been implicated in SUD. The compounds will then be tested for effectiveness in preclinical models of SUD, including models of cocaine, methamphetamine, and fentanyl use. This research has the potential to provide highly impactful and innovative treatment options for SUD via simultaneous modulation of multiple signaling pathways.

This study will conduct preclinical and clinical assessments of the NMDA modulator NYX-783 for treatment of opioid drug-seeking and relapse to opioid use disorder (OUD). NYX-783, a novel small molecule being developed by Aptinyx, has shown evidence of safety/tolerability in Phase 1 studies and is currently in Phase 2 trials for post-traumatic stress disorder. This project will test the safety, tolerability, and pharmacokinetics (PK) of NYX-718 in morphine-maintained patients in residential settings and then conduct a combined inpatient (safety/tolerability/PK) / outpatient (preliminary efficacy) study testing NYX-783’s effects on opioid use and relapse, stress/cue reactivity, craving, and quality of life in OUD subjects maintained on standard extended release naltrexone over a 10-week period. Successful completion of these studies will set the stage for larger scale Phase 2/3 studies of efficacy in OUD that will ultimately be required for FDA approval of NYX-783 for the treatment of drug-seeking and relapse in OUD.