Funded Projects

Although medication-based treatment for opioid use disorder can effectively reduce overdose risk and improve health outcomes, most people discontinue treatment too soon. Quality measures that inform opioid treatment programs about how many patients remain in treatment relative to peer programs could motivate those programs to pursue quality improvement activities, such as helping patients navigate logistical barriers to receiving treatment. This project will test approaches to developing and disseminating retention and outcome measures for opioid treatment programs.

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. 

This site will serve as the Data Coordinating Center for the clinical trial to provide high-quality and impartial biostatistical expertise for all the study sites.

This project creates the HEAL Harm Reduction Network Coordination Center, which will provide support to the nine research studies in the HEAL Harm Research Reduction Network. The center will provide administrative and logistical help; support data harmonization and data sharing; involve stakeholders in all network activities; and share research findings and other products with researchers, practitioners, stakeholders, and the general public. 

The incidence of Neonatal Opioid Withdrawal Syndrome (NOWS) in the United States has increased more than fivefold since 2004 to almost 7 per 1,000 hospital births. It is unknown how these effects are modulated by associated maternal, neonatal, and environmental factors and how the environment, maternal health, and parenting styles modify trajectories of brain connectivity and neurodevelopment. This study leverages the established infrastructure and longstanding collaborations of four clinical sites and the data coordinating center of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network to address current critical knowledge gaps in childhood brain structure and connectivity and on medical, developmental, and behavioral trajectories in early childhood. The study will analyze a well-characterized observational cohort using clinical and neuroimaging measures to improve understanding of the structural and functional sequelae resulting from prenatal opioid exposure and NOWS and their interactions with the maternal-infant dyad.

Neonatal opioid withdrawal syndrome (NOWS) has emerged as a tragic by-product of the opioid epidemic. Newborns whose mothers used opioids while pregnant can experience symptoms of opioid withdrawal in the days following birth, such as tremors, irritability, seizures, sleep, digestive, and feeding problems. However, little is known about the effect of antenatal opioid exposure on longer-term infant development over time. To address this gap in understanding, the ACT NOW Longitudinal study is examining a crucial developmental period from birth to two years of life through a comprehensive battery of assessments, including MRI imaging, neurodevelopmental behavioral assessments, and family report measures. This longitudinal cohort study is projected to include a total of 375 infants, 250 who were exposed to opioids and 125 matched controls.

While some people who use drugs do not carry or use naloxone, others respond to multiple overdoses over short periods of time. This project aims to identify characteristics and experiences of these individuals, known as “overdose responders,” toward better understanding barriers to naloxone use. The research will also test interventions to support the well-being of responders and to increase the number of community members ready and willing to give naloxone to reverse overdose. 

We discovered a class of non-opioid modulators of the T-type Cav3.2 channel that could treat neuropathic pain. In vivo pharmacokinetic and pharmacodynamic studies and preliminary toxicological studies identified AFA-279 and other candidates, which did not produce observable side-effects and showed greater analgesic effects than other neuropathic pain medications in rodent models. The goal of this proposed project is to submit the IND application on our Cav3.2 modulator to the Food and Drug Administration (FDA). We will produce AFA-279 under Good Manufacturing Practice (GMP)–like conditions using chemical manufacturing controls for Good Laboratory Practice (GLP) nonclinical toxicity studies and GMP clinical batch future Phase 1 clinical trials, complete toxicological and safety studies to establish the safety profile of AFA-279, prepare and submit the IND application, and then initiate early clinical trials. Our ultimate goal is to deliver a safer, more effective, non-opioid Cav3.2 channel modulator to patients suffering from neuropathic pain.

Interstitial cystitis/bladder pain syndrome is a debilitating disease affecting many women. Opioid-based pain management is a common feature of current treatment approaches but is associated with the risk of addiction. The causes of this disorder remain unknown, and no effective treatments are available. This project will provide new insights using genetic, medication-based and other approaches in a mouse model, along with single-cell gene expression studies conducted with cells from mice and human patients who have this condition. The analyses will help provide targeted, safe, and effective treatment approaches for individuals with interstitial cystitis/bladder pain syndrome.

The primary cause of death associated with opioids is opioid-induced respiratory depression, and there is currently no way to prevent this condition. The goal of this research is to develop a therapy to prevent opioid-induced respiratory depression without disrupting opioids’ analgesic effects. Previous research has shown that the hormone leptin, which suppresses appetite and increases metabolic rate, also stimulates breathing. This research project in a mouse model will test if the novel, brain-penetrant leptin receptor-binding protein E1/Aca can prevent fentanyl-induced breathing failure without diminishing fentanyl’s analgesic effects.

Chronic low back pain (cLBP) is recurrent and often nonresponsive to conservative treatments. Biomechanists, physical therapists, and surgeons each utilize a variety of tools and techniques to assess and interpret qualitative movement changes to understand potential mechanical and neurological sources of low back pain and as critical elements in their treatment paradigm. However, objectively characterizing and communicating this information is currently impossible, since clinically feasible (i.e., cost-effective, objective, and accurate) tools and quantitative benchmarks do not exist. This research addresses the challenge to improve cLBP outcomes through the use of unique, inexpensive, screen-printable, elastomer-based, nanocomposite, piezoresponsive sensors, which will be integrated into a SPInal Nanosensor Environment (SPINE) sense system to measure lumbar kinematics and provide an objective, quantitative platform for diagnosis, monitoring, and follow-up assessment of cLBP.

This study aims to determine how exposure to opioids and other substances affects the developing fetal brain and shapes later child cognitive outcomes. Researchers will collect neuroimaging and behavioral data, as well as measures of environmental exposures related to social equity, COVID-19, and socioeconomic factors. The project will reduce traditional barriers to participation by using innovative data collection methods and mobile labs to bring the research to underrepresented and marginalized communities. This approach aims to clarify the impact of substance exposure on child development through an equitable approach to research, with generalizable findings. The study will take place at Rhode Island Hospital, where participants will be drawn from a largely rural population.

Individuals who have been previously incarcerated have a significantly higher risk of dying from opioid overdose, particularly in the first two weeks after release. Providing medication for opioid use disorder (MOUD) to individuals on probation or parole decreases the rate of relapse and recidivism, and increases retention in substance abuse treatment. This study will test a systems-change approach for increasing use of MOUD across a network of seven probation and parole sites to improve linkage to the continuum of evidence-based care for justice-involved individuals. Implementation outcomes include program acceptability, adoption, penetration, sustainability, and costs. Client-level effectiveness outcomes include retention, satisfaction, opioid use, opioid overdoses, recidivism, linkage to OUD treatment, and utilization of recovery services. Targeting the intersection of justice and community-based care has substantial potential for addressing the opioid crisis.