Funded Projects

NOFO Title: HEAL Initiative: Novel Targets for Opioid Use Disorders and Opioid Overdose (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-DA-22-031
Summary:

This research project will investigate the cannabinoid receptor 2 protein (CB2R) as a novel therapeutic target for opioid-induced respiratory depression caused by fentanyl, oxycodone, and heroin. This study will shed light on how the endocannabinoid system in the brainstem works to control breathing under normal conditions and during opioid-induced respiratory depression. The research aims to determine whether activation of the CB2R with a brain-penetrant CB2R-binding molecule is safe and clinically useful for treating opioid overdose prevention and reversal. This research will pave the way for discovering new medications that activate CB2R to reduce opioid-related deaths.

NOFO Title: HEAL Initiative: HEAL Data2Action – Innovation and Acceleration Projects, Phased Awards (R61/R33, Clinical Trial Optional)
NOFO Number: RFA-DA-23-057
Summary:

Older adults make up more than half of all surgical patients in the United States, putting them at risk for a range of harmful outcomes including misusing opioids, developing opioid use disorder (OUD), opioid overdose, and surgical complications. This project seeks to understand whether pre-surgery interventions can prevent harmful opioid-related outcomes. The research will combine data from a registry of electronic health records and from Medicare claims data to learn about the relationship between these interventions and opioid-related outcomes including persistent opioid use, OUD, and other harmful outcomes.

NOFO Title: HEAL Initiative: HEALthy Brain and Child Development Study (HEALthy BCD) (Collaborative R34 Clinical Trial Not Allowed)
NOFO Number: RFA-DA-19-029
Summary:

Though prenatal exposure to opioids and other substances have adverse effects on neurodevelopment, advances in neuroimaging and developmentally sensitive phenotypic measurement now enable characterization of typical and atypical brain-behavior pathways on an unprecedented scale. The Brains Begin Before Birth (B4) Midwest Consortium, a partnership of neuroscience, substance use, perinatal mental health, and child welfare scientists at Washington University School of Medicine (WUSM) and neuroscience, bioethics, pediatric population health, maternal-fetal, and addiction scientists at Northwestern University (NU). This regional consortium will leverage the contrasting approaches of Illinois (punitive) and Missouri (non-punitive) to prenatal opioid use, providing a platform for examining the impact of jurisdictional variations on science and practice. The consortium provide a framework for addressing three major areas of challenge: (1) legal/ethical, (2) recruitment/retention, and (3) imaging/assessment methods.

NOFO Title: Pilot Health Services and Economic Research on the Treatment of Drug, Alcohol, and Tobacco Use Disorders (R34 Clinical Trial Optional)
NOFO Number: PA-18-774
Summary:

This study will develop and test the feasibility of implementing guidelines on workplace policies to reduce prescription opioid use, decrease chronic opioid use, promote recovery from opioid use disorder, and improve health-related employment outcomes. The researchers will develop and test these guidelines among construction workers. This project will provide critical information to design and conduct a randomized trial to implement and evaluate insurance and employment policy guidelines among labor-management health funds in the building trades. Aim 1 will identify current best-practice health care and employment policies to prevent health and employment consequences of opioid use. Aim 2 will characterize the opioid problem in construction and adapt best-practice healthcare and employment policies to the unique needs of the construction industry. Aim 3 will evaluate the feasibility of implementing workplace opioid guidelines in the construction trades and will define and collect measures of implementation and effectiveness.

NOFO Title: HEAL Initiative: HEALthy Brain and Child Development Data Coordinating Center (U24)
NOFO Number: RFA-DA-21-023
Summary:

The HEALthy Brain and Child Development National Consortium (HBCD-NC) Data Coordinating Center (HDCC) will provide data management and oversight to all HBCD-NC sites to ensure the consortium’s primary objective of establishing a normative template of developmental trajectories over the first 10 years of life is met. The HBCD-NC will collect neural, behavioral, physiological, and psychological measures, as well as biospecimens, to characterize neurodevelopmental trajectories. The HDCC will coordinate data collection, data quality, data harmonization, data sharing, and data analysis efforts that are central to the consortium’s ability to implement a common research protocol. The HDCC will assemble all data across the consortium sites and distribute a comprehensive and well curated research dataset to the scientific community at large. The HDCC is tightly integrated with the HEALthy Brain and Child Development Administrative Core (HCAC) and includes a multi-institution investigative team at the University of Minnesota, University of California, San Diego, and Washington University at St Louis.

NOFO Title: HEAL Initiative: Justice Community Opioid Innovation Network (JCOIN) Clinical Research Centers (UG1 Clinical Trial Optional)
NOFO Number: RFA-DA-19-025
Summary:

A major driver of the U.S. opioid crisis is limited access to effective medications for opioid use disorder (MOUD) that reduce the risk of overdose. Traditionally, jails and prisons in the U.S. do not initiate or maintain MOUD for inmates with OUD prior to their return to the community, which places them at high risk for fatal overdose. The Massachusetts Justice Community Opioid Innovation Network (JCOIN) will study the outcomes and implementation of a 2018 state law that seven county jails must provide all approved forms of medication for OUD. The Chapter 208 initiative has important implications for future policy and practice in the justice and OUD treatment systems at the local, state, and national levels.

NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: RFA-DA-19-002
Summary:

There is a need for longer-acting prophylactic pharmacologic options for opioid use disorder (OUD) patients during maintenance therapy. This study tests a titanium implant loaded with a formulation of naltrexone and a naturally occurring carboxylic acid. The device is implanted subcutaneously with local anesthetic during an in-office procedure. The technology is based on a unique formulation that keeps the pH within the reservoir low and promotes passive diffusion of naltrexone. The benefits of the product include complete medication adherence for one year after administration, fewer relapses, smooth profile ensuring complete prophylaxis without sub-therapeutic plasma troughs, full reversibility, and similar efficacy with less drug exposure. This technology has been validated clinically with another drug and tested preclinically with naltrexone. This project will finalize the chemistry manufacturing and controls, produce IND supplies, conduct an IND-enabling safety study, and submit the IND.

NOFO Title: HEAL Initiative: HEALthy Brain and Child Development Study (HEALthy BCD) (Collaborative R34 Clinical Trial Not Allowed)
NOFO Number: RFA-DA-19-029
Summary:

Despite increased efforts to understand the neurodevelopmental sequelae of in utero opioid and other substance exposure on long-term behavioral, cognitive, and societal outcomes, important questions remain, specifically, 1) How is brain growth disrupted by fetal substance and related pre- and post-natal exposures? and 2) How are these disrupted growth patterns causally related to later cognitive and behavioral outcomes? This project seeks to formulate an approach to addressing these key questions and decipher the individual and cumulative effect of these intertwined pre- and post-natal exposures on child neurodevelopment. First, researchers will address the legal, ethical, and mother-child care and support concerns implicit in this study. Next, they will integrate across our areas of neuroimaging expertise to develop, implement, and harmonize a multi-modal MRI and EEG protocol to assess maturing brain structure, function, and connectivity. Finally, researchers will develop and test advanced statistical approaches to model and analyze this multidimensional and longitudinal data.

NOFO Title: HEAL Initiative: America’s Startups and Small Businesses Build Technologies to Stop the Opioid Crisis (R43/R44 - Clinical Trial Optional)
NOFO Number: RFA-DA-19-019
Summary:

Opioid agonist therapy (OAT), such as buprenorphine/naloxone (BUP/NAL), is proven effective against opioid use disorder (OUD), but poor medication adherence is a major barrier. This project aims to substantially increase adherence to oral BUP/NAL with Pillsy, a smart technology platform, which acts like a digital medication coach, providing education and reminders using a mobile app, text messages, and automated phone calls. The platform is built around a Bluetooth-based smart pill bottle cap that automatically tracks doses and timing, and sends intelligent reminders to create a unique feedback loop, which allows constant optimization of the incentive/reminder messages to meet user needs to increase adherence. A dashboard enables providers to easily track medication use and patient engagement. The Pillsy platform only nominally increases the cost of oral BUP/NAL treatment, and physicians can bill for monitoring time (CPT code 99091). The project team will adapt the current Pillsy platform and perform a randomized efficacy trial of BUP/NAL adherence.

NOFO Title: HEAL Initiative: HEAL Data2Action Innovation Projects (R61/R33 Clinical Trial Optional)
NOFO Number: RFA-DA-22-051
Summary:

This project will use a data-to-action framework to guide implementation of opioid use disorder treatment and harm reduction interventions based on rapid data analysis. It will leverage existing data systems such as Emergency Medical Services (EMS) reports, mobile integrated health case management data, and medical examiner data for near real-time data analyses, visualization, and action planning. This research will collect a range of data (opioid treatment, use of acute care services, morbidity, mortality, incarceration, housing support, and cost benefits) from a sub-acute stabilization center for people at high risk for opioid overdose, including those who have recently overdosed and are referred and transported by EMS teams.

NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-18-591
Summary:

People who use opioids in rural areas suffer worse health and less insurance coverage. The opioid problem in rural areas is of particular concern, as rural areas have higher overdose rates despite equivalent rates of OUD. This is because rural areas have a scant number of clinics and clinicians who provide medication treatment for OUD. Thus, people living in rural areas must travel long distances to access clinics that may or may not have expertise in providing treatment to patients with OUD. Telemedicine (TM) could efficiently increase capacity for delivery of buprenorphine in rural areas and may increase the number of patients receiving medication treatment and improve treatment retention and outcomes. While the development of medication treatments for opioid use disorder (MOUD) capacity in primary care settings with optimal/comprehensive services is desirable, the current opioid crisis with escalating overdose death rates in rural areas suggests a need to implement an efficient, cost-effective system of MOUD services that can be scaled up quickly. The use of a centralized and Medicare-covered TM vendor utilizing a developed methodology and established organizational infrastructure offers the great potential for a rapid rollout to increase access to MOUD and improve treatment retention in rural areas. This cluster randomized clinical trial with two phases will test expanded treatment access to improve retention on MOUD in highly affected rural areas. Phase I will include implementing telemedicine in a limited number of rural sites with varying levels of office-based opioid treatment (OBOT) to inform implementation strategies for the main trial, and Phase II will include evaluate comparative effectiveness between OBOT alone and OBOT + TM at 30 sites.

NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-18-591
Summary:

The U.S. is in the midst of a devastating opioid epidemic. Since 1999, the number of overdose (OD) deaths involving opioids has quadrupled. These trends are magnified among American Indians/Alaska Natives (AI/ANs) compared to other racial/ethnic groups. AI/ANs are second only to Whites in the rate of OD mortality (8/100,000 versus 12/100,000 deaths, respectively). Medications for opioid use disorder (OUD; i.e., methadone, buprenorphine and naltrexone) are considered the most effective treatment, reducing mortality and increasing abstinence and retention. However, numerous barriers limit the uptake of medications for OUD in tribal communities and within urban treatment settings serving AI/AN individuals. This is a two-phase formative research study to develop and test an implementation intervention for programs to provide medications to treat OUD specifically with AI/AN consumers. The objective of Phase I (12 months) is to develop a culturally centered implementation intervention to integrate medications for opioid use disorder (MOUD) into health care/addiction specialty settings. The objective of Phase II (24 months) is to conduct a preliminary test of the implementation intervention at four sites serving AI/AN communities. Community-based participatory research (CBPR) methods will be used throughout both phases. This study will help with decreasing stigma and increase the utilization of MOUD in health care settings that serve AI/AN populations.

NOFO Title: HEAL Initiative: Effectiveness Trials to Optimize, Implement, Scale, and Sustain the Collaborative Care Model for Individuals with Opioid Use Disorders and Mental Health Conditions (U01 Clinical Trial Required)
NOFO Number: RFA-MH-19-525
Summary:

Medication-assisted treatment (MAT) represents the gold-standard intervention for opioid use disorder (OUD). However, only 20% of Americans with OUD received any formal or informal addiction treatment in the past year. Lack of access and engagement in MAT is driving poor OUD outcomes, especially in rural areas lacking specialty addiction services. The Advancing Integrated Mental Health Solutions (AIMS) Center at the University of Washington has successfully helped over a thousand primary care clinics across the country implement collaborative care for mental health disorders. The study will determine whether collaborative care can be used to successfully treat mental health disorders and OUD concurrently in primary care settings. Clinics offering collaborative care will randomize sites to add OUD to their collaborative care program or remain unchanged. Clinics not offering collaborative care will randomize sites to implementing collaborative care for OUD and mental health disorders simultaneously or for mental health disorders only.