Funded Projects

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:

Methadone maintenance therapy has been shown to facilitate recovery and prevent deaths from opioid use disorder (OUD). This proposal is for development of a once-weekly oral methadone for maintenance therapy for OUD. Lyndra has developed an oral gastric residence dosage form that has been demonstrated to provide at least seven days of continuous delivery. A once-weekly oral methadone product could lower a major barrier to treatment for many patients, reduce the stigma and socioeconomic impact of medication-assisted therapy, and increase the capacity of methadone treatment centers by reducing the number of patient visits. This study will perform pharmaceutical development and pharmacological characterization of a once-weekly oral methadone dosage form, leading to the selection of a clinical candidate for a first-in-human trial and submission of an IND. Clinical trials will then be performed to evaluate the safety and pharmacokinetics of the once-weekly oral methadone dosage form in subjects with OUD.

NOFO Title: HEAL Initiative: Harm Reduction Policies, Practices, and Modes of Delivery for Persons with Substance Use Disorders (R01 Clinical Trial Optional)
NOFO Number: RFA-DA-22-046
Summary:

Harm reduction supplies include fentanyl test strips that allow people who use drugs to identify whether the substance(s) they plan to take contain fentanyl and sterile syringes that help to prevent the spread of infectious diseases among people who inject drugs. One potential way to increase access to harm reduction supplies is mail delivery. This project will describe state-level policies that deter the use of mail-based delivery of harm reduction services, examine characteristics of people who use mail-based harm reduction services, and assess individual preferences related to mail-based harm reduction services.

NOFO Title: HEAL Initiative: Development of Therapies and Technologies Directed at Enhanced Pain Management (R43/R44 – Clinical Trial Not Allowed)
NOFO Number: RFA-NS-20-011
Summary:

About 14% of U.S. adults report experiencing migraine symptoms within any given 3-month period, making it the second most disabling illness in the world. Nonspecific pain medications used in migraine (e.g., acetaminophen, nonsteroidal inflammatory drugs, opioids) are often not effective for severe migraine symptoms or cause significant adverse effects. A research team of migraine care specialists, device and drug developers, and clinical research specialists has created a technology for accurately delivering self-administered migraine medication to the upper nasal cavity. The technology enables development of a self-administered therapy to provide rapid pain relief without harsh and addictive side effects of existing migraine medications. This project will establish efficacy and evaluate commercial design feasibility for this treatment.

NOFO Title: HEAL Initiative: Multilevel Interventions to Reduce Harm and Improve Quality of Life for Patients on Long Term Opioid Therapy (MIRHIQL): Resource Center (U24- Clinical Trial Optional)
NOFO Number: RFA-DA-23-042
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. The MIRHIQL Resource Center will provide infrastructure support for the network as well as create a risk-benefit decision tool to help providers determine when opioids should be continued as prescribed, tapered, or tapered/discontinued. The center will first develop and validate a clinical definition for individuals who take long-term opioids, then study long-term outcomes in participants who receive treatment in primary care settings. This research will partner with many groups including individuals with lived experience, community health care providers who treat such individuals, research scientists, bioethicists, and professional societies

NOFO Title: HEAL Initiative: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)
NOFO Number: NS22-034
Summary:

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.

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:

There is little evidence available to guide clinical care for patients on long-term opioid therapy for whom risks exceed benefits. Given valid fears about both pain and withdrawal during decreased dosing (tapering), these individuals face challenges, including concerns about being abandoned by providers and uncertainty about the need to discontinue opioids. As such, these patients are hesitant to enroll voluntarily in opioid discontinuation research, further deepening the clinical evidence gap. This project will evaluate three effective and scalable interventions for individuals on long-term opioid therapy: (1) low-dose transdermal buprenorphine (without) of opioid withdrawal, (2) a brief cognitive behavioral intervention for pain, and (3) noninvasive brain stimulation.

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

Hospital inpatient stays due to opioid-related health problems are a reachable moment for increasing access to treatment with medications for opioid use disorder (MOUD). Hospitalized patients with opioid use disorder (OUD) are at particularly high risk for morbidity, mortality, and high medical costs in the U.S. This study will substantially inform the care management of OUD in hospitalized patients. The project includes a comparative effectiveness research trial and an implementation research trial, which will lead to models of broad dissemination for treatment approaches to this largely unaddressed population. They will examine whether (1) in hospitals with addiction medicine consultation services, hospital-initiated extended-release buprenorphine (XR-BUP), compared with other OUD medications, results in increased engagement in treatment with MOUD following hospital discharge and (2) training hospitals without such consultation services on best practices for initiating MOUD using consultation service hubs improves medication uptake in hospitals and increased MOUD treatment engagement following discharge.

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

This health care data mining study analyzes existing Veterans Health Administration data sets to examine patient and organizational characteristics associated with buprenorphine termination during outpatient OUD treatment. This project will generate data useful for predictive modeling on how to implement targeted approaches to improve retention in OUD treatment. An objective is to identify patient, provider and system targets to reduce unnecessary or inappropriate discontinuation of buprenorphine care. These analyses are critical for establishing initial constructs to evaluate reasons for treatment discontinuation based upon patient, provider and system factors in different health care settings.

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

There is a significant treatment gap between patients diagnosed with OUD and those who seek treatment, and only a small proportion of those seeking treatment receive MOUD. Primary care is the most common point of health care contact in the U.S. and is an important venue to address stigma, improve access to treatment and improve quality of care. Over the past decade, electronic health record (EHR)-linked Web-based point-of-care clinical decision support (CDS) systems designed to improve quality of chronic disease care have become increasingly sophisticated and successful. A Web-based and EHR-integrated OUD CDS system to offer expert guidance to primary care providers (PCPs) on the diagnosis and management of OUD was developed and piloted. This project will implement the OUD clinical decision support system in three large diverse health care systems and randomize a minimum of 30 clinics to receive the OUD-CDS intervention or usual care (UC). The project will evaluate the impact of OUD CDS on practice process measures and patient outcomes. The study will also prepare for scalability and dissemination by evaluating facilitators and barriers to implementation, determining the costs of implementation and maintenance and assessing the short-term cost impacts of the OUD-CDS.

NOFO Title: HEAL Initiative: Notice of Special Interest (NOSI) regarding the Availability of Administrative Supplements to Support Strategies to Reduce Stigma in Pain Management and Opioid Use Disorder (OUD) and Treatment
NOFO Number: NOT-OD-20-101
Summary:

Increasing primary care clinician intention and behavior to obtain waivers to prescribe buprenorphine for treatment of opioid use disorder and increase use of the Opioid Wizard, a clinical decision support tool, has potential for patient benefit. This supplement will provide support to evaluate a training tool as an intervention to reduce stigma in primary care clinics by integrating a stigma reduction training component into the Opioid Wizard training at multiple sites of the NIDA Clinical Trial Network. Primary care providers will be randomized to novel stigma reduction training, grounded in stigma science, or an attention-control training to determine whether stigma reduction training reduces provider stigma, increases intention to apply for a waiver to prescribe buprenorphine, and ultimately increase the likelihood that providers use Opioid Wizard. The proposed supplement will utilize the randomized controlled trial design embedded in the larger multisite trial to evaluate the Opioid Wizard tool to help primary care clinicians identify, diagnose, and treat patients with opioid use disorder while evaluating the effect of the stigma reduction training.

NOFO Title: Notice of Special Interest to Encourage Eligible NIH HEAL Initiative Awardees to Apply for PA-18-906 Research Supplements to Promote Diversity in Health-Related Research (Admin Supp - Clinical Trial Not Allowed)
NOFO Number: NOT-NS-20-023
Summary:

A current obstacle to developing more effective therapies for chronic low back pain is the lack of clinical trials assessing the feasibility and potential effectiveness of promising new targets for neuromodulation. This project will explore the feasibility of using deep brain stimulation of a new brain target for treating chronic low back pain. The study will also explore imaging biomarkers in patients with chronic low back pain that can be used to predict whether someone is a candidate or may respond to deep brain stimulation therapy, to guide programming and patient selection for this therapy in the future.

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: HEAL Initiative: Antenatal Opioid Exposure Longitudinal Study Consortium (PL1 Clinical Trial Not Allowed)
NOFO Number: RFA-HD-19-025
Summary:

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.