Funded Projects

NOFO Title: HEAL Initiative: Translating Research to Practice to End the Overdose Crisis (R61/R33 Clinical Trial Optional)
NOFO Number: RFA-DA-23-053
Summary:

People who survive sexual violence are at increased risk for posttraumatic stress disorder (PTSD) and opioid misuse. Emergency departments are often the first, and in some cases only, contact with the medical care system for survivors of sexual violence. This makes them a suitable setting to initiate interventions to address the risk of PTSD and opioid misuse in these individuals. This project will develop and test a brief, low-cost video and text message intervention that can be initiated in the emergency department to prevent onset or escalation of PTSD and opioid misuse among people who survive sexual violence.

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

For many reasons, the emergency department (ED) is a critical venue to initiate opioid use disorder (OUD) interventions. ED patients have a disproportionately high prevalence of substance use disorders and are at an elevated risk of overdose, and many do not access health care elsewhere. Despite this, OUD interventions are rarely initiated in EDs. The Emergency Department Connection to Care with Buprenorphine for Opioid Use Disorder study (CTN-0079) will assess the feasibility, acceptability and impact of introducing clinical protocols for screening for OUD, buprenorphine treatment initiation, and referral for ongoing treatment in ED settings with high need, limited resources and different staffing structures. This extension study will use the existing infrastructure to evaluate the adoption and sustainability of the clinical protocols introduced at each of the study sites and to identify factors influencing their diffusion and effectiveness.

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:

Opioid use disorders (OUD) are a national public health emergency with more than 115 fatal overdoses occurring each day in the U.S. and an economic burden of more than $78 billion a year. Several medications are available for treating OUD, but their access is limited and efficacy is often sub-optimal. It is thus urgent to develop new, affordable strategies for the effective treatment of OUD. Immunopharmacotherapy has emerged as a promising treatment approach against OUD that relies on the induction of drug-specific antibodies to neutralize circulating drug molecules and reduce or cancel their effects. Several groups have attempted to apply this strategy with mixed results, suggesting that novel immunization platforms must be tested to further improve vaccine efficacy against OUD. This project will fabricate novel nanoparticle-based vaccines against OUD that are likely to boost their immunogenicity and lead to a more robust and effective immune response against the target opioid. The broad impact of this project resides in the rational design of nanoparticle-based vaccines that are safe and effective against opioids. This novel nanoparticle-based immunization strategy can be applied to the development of next-generation vaccines against a range of OUD and other substance use disorders.

NOFO Title: Notice of Special Interest to Encourage Eligible NIH HEAL Initiative Awardees to Apply for PA-20-222: Research Supplements to Promote Diversity in Health-Related Research (Admin Supp - Clinical Trial Not Allowed)
NOFO Number: NOT-NS-20-107
Summary:

Most opioid misuse begins during adolescence and young adulthood. Adolescence is the best time for prevention interventions in settings like school-based health centers (HCs), yet few programs focus on preventing initiation of opioid misuse. This study harnesses the power of video game interventions and incorporates components of effective substance use prevention programs to develop an evidence-informed intervention to prevent the initiation of opioid misuse in adolescents. In partnership with the national School-Based Health Alliance (SBHA), researchers will develop and test a new video game intervention, PlaySmart. It will build on our previous video game intervention that has demonstrated efficacy in improving attitudes and knowledge related to risk behaviors. The study will evaluate the game in a randomized controlled trial in 10 school-based HCs and examine strategies for implementing PlaySmart in school-based HCs nationally. This research has considerable potential for wide implementation, reach, and impact on high-risk adolescents through school-based HCs.

NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: PAR-20-092
Summary:

An increasing number of Americans use multiple drugs at the same time, and overdose deaths from stimulants have increased. However, there are no available treatments for stimulant use disorder. This project aims to develop new treatment (SBS-518) for cocaine use disorder. Previous research using animal models showed that SBS-518 decreases stimulant self-administration without being rewarding itself. The research will continue the development of SBS-518 toward testing in human research participants.

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: PHS 2018-02 Omnibus Solicitation of the NIH, CDC, and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed)
NOFO Number: PA-18-574
Summary:

Rescue of victims of opioid overdose is accomplished by treatment with antagonist drugs, such as naloxone, that can reverse the respiratory depression. However, naloxone has serious liver toxicity and a short half-life, and its complete antagonism results in a withdrawal effect. Nalmefene is an FDA-approved opioid derivative that is an antagonist of the MOR and a weak agonist of the k-opioid receptors (KOR). An immediate release intravenous injectable formulation was approved by the FDA in 1995 for opioid overdose; however, the requirement for intravenous administration has limited its clinical use. This project, in partnership with Avior, aims to develop a fast-onset, rapidly-dissolving, mucoadhesive thin film formulation that carries uniformly distributed nalmefene nanoparticles on the surface of the film. This film, produced using Avior’s proprietary Speedit™ transmucosal drug delivery technology, rapidly delivers nalmefene when the film is placed in contact with the lower lining of the inner lip. This project will generate non-clinical data to support critical human clinical trials to determine if a transmucosal film can be developed with a rapid onset of action that is required for rescue of opioid overdose patients or taken prophylactically to prevent respiratory depression, to assess whether the effective speed of delivery is sufficient to conduct a human clinical trial.

NOFO Title: HEAL Initiative: HEAL Data2Action Innovation Projects
NOFO Number: RFA-DA-22-051 
Summary:

Clinical decision support tools help clinicians make treatment decisions based on routinely collected data and offer a promising strategy to implement evidence-based practices for safe and effective pain management. This project will use clinical decision support tools embedded into electronic health records to help healthcare providers make treatment decisions that align with opioid prescribing guidelines from the Centers for Disease Control and Prevention (CDC). The project will also use information from prescription drug monitoring programs, insurance claims, and mortality data to evaluate patient outcomes. This research will evaluate how prescribing practices that align with CDC guidelines affect patient outcomes and whether clinical decision support tools provide an advantage over standard care practices for pain management.

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

Effective treatment for OUD has been shown to improve patient outcomes and reduce health care costs; however, evidence of this effect in primary care settings is severely limited. The health economic findings from this study will supplement the parent PROUD trial’s results regarding clinical effectiveness and implementation outcomes and provide critical contextual information for health systems and other health care stakeholders. The study will evaluate the economic viability of the PROUD collaborative care model for OUD—that is, from the perspective of the health care sector, to what extent do the downstream cost savings associated with improved patient outcomes offset the additional costs of the PROUD intervention? The specific aims are to (1) estimate the start-up and ongoing management costs of the PROUD intervention, (2) assess costs associated with health care utilization for patients who receive primary care treatment in PROUD and usual care clinics and have been identified with recognized OUDs before clinic randomization, and (3) estimate the economic value of the PROUD intervention, measured as net monetary benefit (NMB, incremental benefit minus incremental cost), from the health care sector perspective.

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:

Addiction to opioids is related to the physiology of the brain’s dopamine-based reward system. As a modulator of dopaminergic systems, the neurotensin 1 receptor (NTR1) should be a molecular target for treating addictive disorders; however, few non-peptide brain penetrant neurotensin modulators have been identified, and orthosteric NTR1 ligands display side effects that have limited their clinical development. This group discovered a series of brain-penetrant NTR1 modulators, including a lead compound SBI-553, with a unique mechanism of action at NTR1. SBI-553 is an orally available, brain penetrant ?-arrestin biased allosteric modulator of NTR1, which shows efficacy in a range of addiction models and circumvents the clinically limiting side effects. While potentially high risk, the activity of SBI-553 has been validated in vitro and in vivo, and the initial safety profiling indicates no issues that would preclude further development. This study will develop SBI-553 as a treatment for opioid use disorder.

NOFO Title: HEAL Initiative: Notice of Special Interest (NOSI) regarding the Availability of Administrative Supplements to Support Strategies to Increase Participant Diversity, Inclusion and Engagement in Clinical Studies
NOFO Number: NOT-NS-21-025
Summary:

The emergency department is an ideal venue to reach and intervene with adolescents and young adults at risk for opioid misuse, particularly as young adults may disconnect from primary care when transitioning out of care in pediatric settings. This study will evaluate the efficacy of interventions of varying type and intensity to prevent or reduce opioid misuse or opioid use disorder. 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 emergency department 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 coaches allow for real-time tailoring to the rapidly changing opioid epidemic, with the potential to prevent an increase in opioid misuse among adolescents and young adults.  Black/African American youth are at increased risk for opioid and other substance use, but they often do not participate in research studies. As a result, it is not known how well prevention interventions work with Black/African American people. This supplement will focus on increasing participant diversity and inclusion by recruiting additional Black/African American participants for this ongoing randomized controlled study of technology-driven prevention interventions.

NOFO Title: HEAL Initiative: Multilevel Interventions to Reduce Harm and Improve Quality of Life for Patients on Long Term Opioid Therapy (MIRHIQL) (R01 Clinical Trial Required)
NOFO Number: RFA-DA-23-041
Summary:

Decreasing opioid dosing faster than advised by clinical recommendations often leaves chronic pain unaddressed and may increase the risk of overdose and suicide compared to continuing long-term opioid treatment. This project will compare a patient-centered tapering protocol with or without MORE in primary care offices in New Jersey and Utah. The MORE approach integrates training in mindfulness, reappraisal, and savoring to alter behavior away from valuation of drug rewards and toward natural rewards. This research will also identify practices to use MORE in primary care settings.

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.