Funded Projects

There is an urgent need to prevent and reduce opioid use disorder (OUD) by reducing the need for opioid analgesia and preventing the escalation of opioid dosing in patients at greater risk of using more opioids following surgery. Brivoligide is a non-opioid drug candidate that can alter the course of postoperative pain for patients most likely to suffer increased pain and utilize more opioids following surgery. A single administration of brivoligide at the time of surgery can reduce acute postoperative pain in these patients by 30 percent to 40 percent beyond what can be achieved with the current standard of care for at least 28 days and reduce opioid utilization by 40 percent over a 3-month period following surgery. This project will support the research necessary to achieve regulatory approval of brivoligide with a broad indication, which will initially focus on the reduction of postoperative pain following mastectomy, a soft-tissue surgery model suitable to detect long-term pain and opioid reduction benefits. Brivoligide appears to be a very promising pharmacotherapy with the potential to greatly contribute to stemming the tide in the opioid crisis.

The goal of this proposal is to launch an innovative, multi-modal neuroimaging program that will investigate the longitudinal trajectory of the neurodevelopment of irritability across the preschool period. Differentiating clinically salient irritability from developmentally normative temperamental variation has proven to be a difficult task. This is made even more challenging during the preschool period, when irritability has hit its normative peak and measuring neurodevelopment is impeded by methodological constraints. This research will (1) identify specific biomarkers underlying preschool vulnerability for psychopathology by examining neural maturation in executive function as a predictor for clinical outcome; and (2) examine how the parenting environment moderates this vulnerability, with the overarching objective of identifying aberrant irritable trajectories as the foundation for future brain-based behavioral intervention. Primary analyses will (1) probe underlying executive function as a predictor of clinical outcome; and (2) examine parent-child neural synchrony as a predictor of executive function maturation.

Pain is one of the most common and debilitating symptoms of a wide range of injuries and diseases. Safe and effective alternatives for treating pain that reduce dependence on opioids are, therefore, a primary goal of the NIH. This project proposes a non-invasive, non-pharmacological alternative to treat pain by combining an innovative electroencephalography (EEG)-based Neurofeedback (NF) solution in an immersive virtual reality (VR) environment. NF and VR have been shown to independently produce ameliorative effects on pain, and it is hypothesized that an NF training in VR would have synergistic effects, as VR would distract from pain perception to improve patient compliance in more engaging NF protocols that improve their ability to control pain perception. In the scope of this project, we will initially focus our work on chronic low back pain (cLBP), as this is a growing segment of chronic pain sufferers with a 39 percent worldwide lifetime prevalence, and whose sufferers have historically been heavy users of opiates; later stages of this project will expand this application to address other forms of pain.

This proposal aims to test the impact of an empirically derived implementation strategy—under real-world conditions and across multiple child service systems—on successful adoption and sustainment of two evidence-based programs that address adolescent substance abuse: Treatment Foster Care Oregon (TFCO; formerly Multidimensional Treatment Foster Care) and Multidimensional Family Therapy (MDFT). The overarching goal of this proposal is to evaluate whether the integration of implementation fidelity (fidelity to the implementation process) with intervention fidelity (fidelity to the clinical intervention) can increase the probability that a new organizational site not only successfully adopts a program but develops the infrastructure to ensure it can sustain. This study will (a) evaluate the effect of stages of implementation completion coaching strategy (SIC-CS) on outcomes of program adoption and sustainment, (b) extend the SIC to include measurement of sustainment, and (c) examine cost and resource patterns most likely to yield sustainable programs.

A more than 5-fold increase in the incidence of neonatal abstinence syndrome has been reported since 2000. Preliminary studies show that prenatal opioid exposure is associated with increased risk of impaired neurodevelopment. Five institutions (Duke University, Arkansas Children’s Research Institute, Cincinnati Children’s Hospital, University of Illinois at Urbana–Champaign, and University of North Carolina at Chapel Hill) have formed a consortium to develop strategies for the Phase II HEALthy Brain and Child Development Study. Research teams will develop instruments and strategies (recruitment/retention protocols, assessment batteries, and novel tools); conduct pilot studies (fetal and postnatal imaging, advanced imaging harmonization and quality control, assessment administration, biosampling) to evaluate instruments; and analyze available data, including imaging, behavioral, cognitive, and maternal data from studies on early brain development, to guide the Phase II study design. Upon completion, the consortium aims to conduct the Phase II study.

More than 100 million adults in the U.S. suffer from intermittent or constant chronic pain, and chronic pain affects at least 10 percent of the world’s population. The primary pharmaceuticals for treatment of chronic pain have been natural or synthetic opioids, and the use of opioids for pain treatment has resulted in what has been called an “epidemic” of opioid abuse, addiction, and lethal overdoses. Through a process of rational drug design, the research team has generated a new chemical entity (NCE) and have given it the name Kindolor, a non-opiate, non-addicting molecule that was shown to reduce or eliminate chronic pain in five animal models at doses compatible with use of Kindolor in humans. This project intends to complete the pre-clinical studies required for an IND application, which, if approved, would allow for proceeding onto the Phase 1 and 2 studies to assess safety and efficacy of the compound against osteoarthritic pain.

Emergency department (ED)-initiated buprenorphine/naloxone (BUP) with referral for ongoing BUP is superior to referral alone in engaging patients with untreated opioid use disorder (OUD) in treatment at 30 days and is cost-effective. However, logistical barriers exist in translating research into practice. New BUP formulations such as the extended-release injectable BUP (CAM2038, XR-BUP) hold promise in addressing many of the barriers more effectively than sublingual buprenorphine (SL-BUP) by treating the patients’ symptoms for up to seven days. This study will recruit, train and provide resources to 30 ED sites throughout the U.S. using implementation facilitation strategies to address stigma and provide ED-initiated BUP for patients presenting with OUD who are not receiving medications for OUD. Once implementation is adequately achieved, the sites will conduct a randomized controlled trial (RCT) to compare the effectiveness of SL-BUP versus XR-BUP on ED patients’ engagement in formal addiction treatment seven days after their ED visit. In addition, in an ancillary component of the study, the use of XR-BUP will be assessed in ED patients with Clinical Opioid Withdrawal Scale (COWS) scores of

Emergency department (ED)-initiated buprenorphine/naloxone (BUP) with referral for ongoing BUP is superior to referral alone in engaging patients with untreated opioid use disorder (OUD) in treatment at 30 days and is cost-effective. However, logistical barriers exist in translating research into practice. New BUP formulations such as the extended-release injectable BUP (CAM2038, XR-BUP) hold promise in addressing many of the barriers more effectively than sublingual buprenorphine (SL-BUP) by treating the patients’ symptoms for up to seven days. This study will recruit, train and provide resources to 30 ED sites throughout the U.S. using implementation facilitation strategies to address stigma and provide ED-initiated BUP for patients presenting with OUD who are not receiving medications for OUD. Once implementation is adequately achieved, the sites will conduct a randomized controlled trial (RCT) to compare the effectiveness of SL-BUP versus XR-BUP on ED patients’ engagement in formal addiction treatment seven days after their ED visit. In addition, in an ancillary component of the study, the use of XR-BUP will be assessed in ED patients with Clinical Opioid Withdrawal Scale (COWS) scores of

Levo-alpha-acetylmethadol (LAAM) offers numerous behavioral and clinical advantages for select opioid use disorder (OUD) patients who do not respond to standard treatment. While LAAM was withdrawn from the market despite being approved for OUD treatment, this project seeks to develop novel, patentable, convenient dosage forms of LAAM, including novel LAAM oral dosage formulations and novel buccal film formulations of LAAM. Morphology, mechanical property, drug release kinetics, and stability of the oral dosage and buccal film formulations will be characterized to determine the instant release or steady release of LAAM, respectively. The two lead LAAM formulations with adequate release and stability profiles will be chosen through optimization studies both in vitro and in vivo. A human pharmacokinetic/pharmacodynamic study will then be carried out on the two selected formulations.

Many individuals with opioid use disorder pass through the criminal justice system over the course of their life. Improved access to high-quality, evidence-based addiction treatment in justice settings is critical to addressing the opioid crisis. The Justice Community Opioid Innovation Network (JCOIN) is studying approaches to increase high-quality care for people with opioid misuse and opioid use disorder in justice populations. This research supports a scientist from a group underrepresented in biomedicine to expand capacity of the Mason Coordination and Translation Center that is managing logistics, stakeholder engagement, and dissemination of findings and products from the JCOIN network.

The Great Lakes Node of the NIDA-supported Drug Abuse Clinical Trials Network (CTN) represents all of the major academic medical centers in the Greater Chicago and Wisconsin areas and serves as a vital Midwestern hub for the CTN. This project supports a scientist from a group underrepresented in biomedicine to expand the work of this CTN node on research in several areas. These include mHealth, eHealth, artificial intelligence, natural language processing, and telehealth interventions; focus on youth/adolescent health and seniors/aging; health disparities; and professional education about opioid and substance treatment.