Funded Projects

Neonatal Opioid Withdrawal Syndrome (NOWS) is a condition that occurs when newborns are exposed to opioids during pregnancy. Symptoms often include tremors, excessive crying, sleep deprivation, and swallowing difficulties. Cases are rising, with a newborn affected by NOWS approximately every 15 minutes. Currently, healthcare providers in the United States lack standard, evidence-based treatments for NOWS. 

This project is part of a multi-center, randomized controlled clinical trial that directly compares NOWS treatments—morphine, methadone, and buprenorphine—and takes into account other types of non-drug therapies, such as behavioral interventions. The goal is to generate results that can inform clinical practice guidelines and give newborns with NOWS the best start possible. 

The University of Louisville serves a large, diverse population that is disproportionately affected by the opioid crisis. Mothers and infants treated by the university’s healthcare team live in rural
and urban underserved regions where the frequency of opioid use during pregnancy is among the highest in the country, with a rate estimated at 3 times the national average.

The opioid epidemic in the United States is associated with alarming rates of overdose and overdose deaths. Medication Assisted Treatment (MAT), in combination with psychosocial intervention, is the most effective treatment for OUD; however, many individuals are unable to access treatment, are not sufficiently retained in treatment, or experience barriers that prohibit their participation in treatment. A multipronged approach is needed that includes 1) development of integrated networks of care, both formal and informal, to better address the needs of individuals with OUDs and 2) measures of the efficacy of these integrated networks for addressing the needs of individuals with OUD. This project will build a learning collaborative to address gaps in knowledge about the delivery, sustainability, and assessment of recovery service for individuals on MAT. The collaborative will foster collaboration and communication between stakeholders and with the larger community of research and providers interested in improving the delivery of OUD recovery support services. This community-academic partnership will address the lack of evidence regarding effective recovery support services.

Pain associated with surgery is experienced by millions of patients every year. Although post-surgical pain usually resolves as the surgical site heals, up to half of the patients develop chronic pain after surgery. Opioids remain the mainstay treatment for post-surgical pain which are fraught with serious side-effects and abuse liabilities. The endogenous mechanism that leads to the resolution of post-surgical pain remain unclear, specifically the effects of surgery on the metabolism of sensory neurons and how those changes influence the resolution of post-surgical pain are not known. Preliminary findings suggest that surgical trauma suppresses pyruvate oxidation while increased glutamine catabolism was associated with the resolution of post-surgical pain. This project will test the hypothesis that tissue incision and surgery disrupt the expression of the glutamine transporter ASCT2, which then prevents the resolution of post-incisional pain and aims to validate ASCT2 as a therapeutic target. This project will also employ pharmacological, genetic and animal pain model studies test a novel RNA expression-based strategy to enhance ASCT2 expression in DRG sensory neurons and alleviate postoperative pain in animal model systems. Successful completion of this project would validate ASCT2 as a novel endogenous non-opioid and non-addictive mechanism-based target for the resolution of postoperative pain.

Chronic pain is a major health burden associated with immense economic and social costs. Predictive biomarkers that can identify individuals at risk of developing severe and persistent pain, which is associated with worse disability and greater reliance on opioids, would promote aggressive, early intervention that could halt the transition to chronic pain. The applicant’s team uncovered evidence of a unique cortical biomarker signature that predicts pain susceptibility (severity and duration). This biomarker signature could be capable of predicting the severity of pain experienced by an individual minutes to months in the future, as well as the duration of pain (time to recovery). Analytical validation of this biomarker will be conducted in healthy participants using a standardized model of the transition to sustained myofascial temporomandibular pain. Specifically the biomarker signature will be tested for its ability to predict an individual’s pain sensitivity, pain severity, and pain duration and will perform initial clinical validation.

Chronic pain affects millions of Americans and remains poorly understood and challenging to manage. Researchers do not fully understand brain processes involved in chronic pain, which can vary considerably from person to person. This project will analyze brain function using magnetic resonance imaging (MRI) in individuals with and without chronic pain. The research will also directly determine the degree of pain-related brain imaging changes by using a large database of brain imaging data.

Opioid use disproportionally affects people with co-occurring mental health disorders. Although medication for opioid use disorder (MOUD) is the gold standard of care, engagement rates are low. Also, it is unclear whether addition of one or more behavioral interventions improves outcomes of MOUD treatment, particularly in patients with co-occurring mental health disorders. This project evaluates the effectiveness of the “Maintaining Independence and Sobriety through Systems Integration, Outreach and Networking (MISSION)” intervention—a multi-component, cross-disciplinary, team-based treatment approach that combines three evidence-based practices with MOUD—in people with co-occurring mental health disorders. The 4-year, five-arm, randomized controlled clinical trial will determine the therapeutic benefit of adding MISSION to MOUD and identify the MISSION components that yield the largest clinical improvement and offer the greatest return on investment.

Rapid technological advances are leading to field-deployable mobile sensing devices that can quantify complex dynamics of key physical, biological, behavioral, social, and environmental factors, enabling us to understand causation in complex disorders. Significant new investment is needed to develop and disseminate data analytics tools. The Center of Excellence for Mobile Sensor Data-to-Knowledge (MD2K) will generate generalizable theory, methods, tools, and software to address major barriers to processing complex mobile sensor data and its use in biomedical knowledge discovery and just-in-time care delivery. We will develop and implement a standards-based, interoperable, extensible, and open-source big data software platform for efficient implementation of MD2K data analytics. MD2K will demonstrate the feasibility, utility, and generalizability of this approach by implementing the entire MD2K data analytics system in the context of two biomedical applications: reducing relapse among abstinent daily smokers and reducing readmission among congestive heart failure patients

The growing opioid use epidemic in the U.S. has been associated with a significant increase in the prevalence of pregnant opioid-dependent women and neonatal abstinence syndrome, which is associated with adverse health effects for the infant and with costly hospitalizations. Maintenance with sublingual (SL) buprenorphine (BUP) is efficacious for opioid use disorder but has disadvantages that may be heightened in pregnant women, including the potential for poor adherence, treatment dropout, and negative maternal/fetal effects associated with daily BUP peak-trough cycles. Extended release (XR) formulations may address some of these disadvantages. The primary objective of CTN-0080 is to evaluate the impact of treating opioid use disorder in pregnant women (n = 300) with BUP-XR, compared to BUP-SL, on maternal-infant outcomes. Other objectives include testing a conceptual model of the mechanisms by which BUP-XR may improve maternal-infant outcomes, relative to BUP-SL; determining the economic value of BUP-XR, compared with BUP-SL, to treat OUD in pregnant women; and evaluating the impact of BUP-XR, relative to BUP-SL, on neurodevelopment when the infant/child is approximately 12 and 24 months of age. Ultimately, this study will help in increasing access to treatment as well as provide quality care for pregnant/postpartum women.

Many medication-based and complementary/integrative interventions are available to treat chronic low back pain, yet no treatment works for all patients. This clinical research strives to understand patient characteristics that predict differential responses to chronic low back pain interventions such as acupressure. This knowledge will enable early career researchers and clinicians to develop tailored treatments for individual patients.

Cerebral palsy is the most common physical disability in children. Those who have this condition experience pain throughout their lives. Although opioids are generally not recommended, many adults with cerebral palsy are prescribed them for pain. This project will assess the incidence of chronic pain conditions in adults with and without cerebral palsy as well as measure opioid treatment-related health outcomes in adults with cerebral palsy. This research will also evaluate pain treatment disparities related to race/ethnicity and insurance coverage using national medical claims databases.

Rigorous and impactful clinical pain research requires participant diversity that reflects the racial/ethnic diversity of affected populations. This project will enhance patient and other community engagement, particularly of underrepresented minorities, to participate in clinical research related to the transition of acute to chronic pain.

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.