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. 

Arkansas is a rural state with the second highest opioid prescription rate in the nation and is in the top 3 states nationwide for opioid prescriptions to pregnant mothers. This site has extensive experience in opioid research and conducting multi-center clinical trials. It also provides care to a diverse population.

Stigma is a key barrier to retention in medication-based treatment for opioid use disorder, particularly among low-income, minority individuals. Stigma that exists at multiple levels contributes to poor retention in care, including internalized and anticipated stigma at the individual level, as well as enacted stigma at the health care provider- and community levels. There is an urgent need to develop and evaluate innovative strategies to reduce stigma at these multiple levels among low-income, racial/ethnic minority individuals to improve engagement in care. One of the most promising strategies to reduce multiple intersecting stigmas simultaneously and improve engagement in care for low-income, minority individuals is through the use of peer recovery coaches (PRCs). PRCs, individuals who have gone through the recovery process themselves and are typically state-certified, have been shown to be more acceptable for engaging and retaining low-income, racial/ethnic minority patients in treatment compared to other health workers. However, scarce research has formally evaluated the effects of PRCs on stigma. This study will test how a PRC model can reduce multiple intersecting stigmas among low-income, racial/ethnic minority individuals to improve retention in methadone treatment.

Black/African American and Hispanic/Latino individuals suffer a disproportionate burden of co-occurring substance use and mental illness, in part due to reduced access to culturally responsive quality healthcare, compared to other racial/ethnic groups. In addition, Black/African American and Hispanic/Latino individuals are not well represented in clinical trials that could help reduce these health disparities. This research aims to improve the recruitment of Black/African American and Hispanic/Latino individuals to participate in clinical research related to co-occurring substance use and mental illness. The project will conduct community engagement and community-based participatory research, establishing a bidirectional partnership between researchers and community members.

The emergency department (ED) is an ideal venue to reach and intervene with adolescents and young adults (ages 16-30) at risk for opioid misuse, particularly as young adults may disconnect from primary care when transitioning out of pediatric medicine. This study will evaluate the efficacy of interventions of varying type/intensity to prevent/reduce opioid misuse or opioid use disorder (OUD). The research leverages technology that is appealing to youth to facilitate intervention delivery by health coaches. In this study, adolescents and young adults in the ED screening positive for opioid use or misuse will be randomly assigned to one of four intervention conditions with outcomes measured at 4, 8, and 12 months. Technology-driven, scalable interventions delivered via health coach allow for real-time tailoring to the rapidly changing opioid epidemic, with the potential for a sustainable impact on preventing escalation of opioid misuse among adolescents and young adults.

The HEAL Initiative is establishing a HEAL Data Ecosystem to help investigators manage and share HEAL-generated data. A key principle underlying the HEAL Data Ecosystem strategy is to make those data findable, accessible, interoperable, and reusable (FAIR). Renascence Computing Institute at the University of North Carolina Chapel Hill (RENCI) and RTI, International (RTI) [RENCI/RTI] are serving as the HEAL Data Stewardship Group to guide HEAL investigators as they prepare their data to connect to the HEAL Platform, a secure data access and computing environment that will leverage metadata query to provide access to data and digital assets stored in various disparate repositories. The HEAL Data Stewardship Group is engaging HEAL investigators to understand and enhance data management needs, provide tools, training, and best practices for making data FAIR, and understand and support valuable uses and reuses of HEAL data sharing via the Platform The HEAL Data Stewardship Group will collaborate closely with the HEAL Platform team at the University of Chicago to meet the needs and goals of the HEAL Data Ecosystem.

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.

There is a distinct neural ensemble in the brain that encodes the negative affective valence of pain. This project will identify novel targets to treat pain by determining the molecular identity of these BLA nociceptive cells via in situ hybridization and single cell RNAsequencing (scRNA-seq). Resolving the molecular identity of these ACC nociceptive cells will also reveal new targets to treat pain affect. To achieve these results the project will catalog candidate Gi/o-GPCR targets in BLA and ACC, test their utility to treat pain, and verify these new targets have no effect in the brain?s reward and breathing circuitry. The experiments in this project will also evaluate each target for abuse potential and effects on breathing by using behavioral assays for reward processing and whole-body plethysmography, respectively. To evaluate whether our results in rodents are likely to translate clinically, there will be an analysis of expression patterns of these drug targets in human tissue using in situ hybridization.

The NIH Back Pain Consortium (BACPAC) Research Program brings together leading centers with expertise in studying and treating chronic low back pain to advance understanding of the mechanisms that underlie the condition and to identify novel treatment strategies. BACPAC is undertaking a multisite precision medicine clinical trial taking into account patient-specific information to understand which patients with chronic low back pain respond best to various nonopioid, evidence-based treatments. The trial seeks to enroll a racially, ethnically, and socioeconomically diverse patient population to ensure that the results are applicable to all Americans with chronic low back pain. This project aims to develop comprehensive recruitment and retention plans for study sites that can recruit from historically underrepresented populations in clinical research (e.g., Black and Hispanic populations) and to provide dedicated financial resources to engage patients from these populations using tailored, culturally appropriate strategies.

Researchers at the University of Alabama at Birmingham and the University of Alabama will enroll pregnant women during their second trimester and follow their infants through a comprehensive longitudinal study. This program will follow 300 mother-infant pairs to understand how early life exposure to drugs and other environmental factors affects developmental trajectories. In addition, this program will determine how genetic and biological factors interact with environmental factors to influence neurodevelopment. This study will take place at the University of Alabama at Birmingham, recruiting participants from mainly rural populations with low access to obstetric/gynecological (OB/GYN) care and high rates of substance use.

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 Alabama at Birmingham routinely treats newborns with NOWS and has been part of NICHD’s Neonatal Research Network (NRN) for more than 25 years. The center has an excellent track record of enrollment in clinical studies, with successful follow-up to 2 years of age and beyond.

Peripheral nerve injury-induced upregulation of three axonal guidance phosphoproteins correlates with the development of neuropathic pain through an unidentified mechanism: 1) collapsin response mediator protein 2 (CRMP2); 2) the N-type voltage-gated calcium (CaV2.2); 3) the NaV1.7 voltage-gated sodium channel. Injury induced phosphorylated-CRMP2/CaV2.2 and phosphorylated-CRMP2/NaV1.7 upregulation in the sensory pathway may promote abnormal excitatory synaptic transmission in spinal cord that leads to neuropathic pain states. This project will validate CRMP2 phosphorylation as a novel target in neuropathic pain using innovative tools. Examples include a genetic approach (crmp2S522A) in mice as well as a non-opioid pharmacological approach (a novel CRMP2-phsphorylation targeting compound). Demonstrating that inhibition of CRMP2 phosphorylation reverses or prevents neuropathic pain will promote the discovery and validation of a novel therapeutic target (CRMP2-phosphorylation) to facilitate the development of novel pain therapeutics.

Current practices and culture in treatment programs for opioid use disorder, including treatment with methadone, may contribute to treatment interruption and relapse risk. This project will develop and test a staff-level intervention for opioid treatment programs to increase methadone treatment retention and decrease in-treatment overdose and patient- and staff-reported posttraumatic stress symptoms. The intervention includes components to address trauma in patients and staff as well as separate supervisory structures for counselors/case managers and medical providers.

Many people in jail have both opioid use disorder (OUD) and posttraumatic stress disorder (PTSD). Among people with OUD released from jail, only few engage in treatment and medication therapy once they are back in the community, and opioid overdose is a leading cause of death in this population. This project will test whether identifying and initiating treatment of PTSD in people receiving OUD treatment in jail can increase these individuals’ likelihood of starting and staying in medication treatment after release and thus reduce overdose risk.