Funded Projects

NOFO Title: Loyalty and Reward-Based Technologies to Increase Adherence to Substance Use Disorder Pharmacotherapies (R43/R44 - Clinical Trial Optional)
NOFO Number: RFA-DA-19-014
Summary:

While effective treatments exist for substance use disorders, adhering to treatment and retaining patients in treatment can be a challenge. The objectives of this project are to facilitate the implementation of loyalty/reward-based programs to increase adherence to medical treatment among patients with substance use disorders through innovative solutions to common challenges. Building on experience developing software to promote patient appointment attendance, the project will build a new tool to test on a sample of 10 providers and 10 patients who are prescribed but not fully adherent to substance use disorder treatment. Patients will receive tailored text messages (in English or Spanish) encouraging adherence, self-report their treatment adherence (which will be verified through smart pill caps and biological testing), earn points for adherence that can be exchanged for rewards customized for them based on a baseline survey, and report their satisfaction with the program and process at the end of the 4-week study. This pilot will assess the feasibility and perceived usefulness of the product in support of eventual larger-scale testing in a clinical trial.

NOFO Title: HEAL Initiative: Limited Competition: Resource Coordinating Center for Pragmatic and Implementation Studies for the Management of Pain (PRISM) to Reduce Opioid Prescribing (U24 Clinical Trial Not Allowed)
NOFO Number: RFA-AT-19-011
Summary:

Improved pain management and reduction of opioid use could greatly benefit from improved pragmatic clinical trials (PCTs). The PRISM Resource Coordinating Center (CC), as part of the NIH Health Care Systems Research Collaboratory, will support up to nine more embedded PCTs that address pain management and the opioid crisis. Since 2012, the CC has nurtured 15 Demonstration Projects by providing leadership, resources, tools, training, and coordination of diverse elements. The CC will work collaboratively with each PRISM Demonstration Project team supported through the HEAL Initiative, including their partnering health care systems, to develop, test, and implement the projects while providing technical, design, and coordination support. The CC will also develop and refine technical and policy guidelines and best practices for the effective conduct of pain-related research studies in partnership with health care systems and disseminate best strategies for successful embedded PCTs.

NOFO Title: HEAL Initiative Limited Competition: Behavioral Research to Improve MAT: Ancillary Studies to Enhance Behavioral or Social Interventions to Improve Adherence to Medication Assisted Treatment for Opioid Use Disorders (R01 Clinical Trial Optional)
NOFO Number: RFA-AT-19-007
Summary:

Chronic pain may be linked to poorer outcomes in those using medication-assisted treatments (MAT) to treat opioid use disorders (OUD). Psychosocial interventions for pain have been effective in patients with chronic pain and substance use disorders, but these interventions have not been thoroughly examined in the OUD population receiving MAT. The study team previously refined and adapted a psychosocial pain management intervention (PPMI) to be delivered by telephone for patients with OUD receiving MAT. The current study will understand the potential applicability of this intervention to other high-risk groups, such as veterans, study the longer-term impact of PPMI, and gather data to inform the implementation of PPMI in MAT patients. This work will provide a robust test of the PPMI intervention to help enhance MAT outcomes in a larger and more representative group of participants while also paving the way for future implementation of interventions to improve MAT retention.

NOFO Title: Clinical Trials or Observational Studies of Behavioral Interventions for Prevention of Opioid Use Disorder or Adjunct to Medication Assisted Treatment-SAMHSA Opioid STR Grants (R21/R33)
NOFO Number: RFA-AT-18-002
Summary:

This study proposes to test the delivery of a comprehensive cognitive behavioral therapy, reSET, to determine whether it can improve treatment adherence and long-term outcome among patients with opioid use disorder initiating medication-assisted treatment within a community-based"Hub and Spoke” Model of buprenorphine maintenance in central Pennsylvania. reSET (Pear Therapeutics, Inc.) is a commercially available version of the web-based Therapeutic Education System (TES) delivered as a mobile app and recently approved by the FDA as the first digital therapeutic adjunct for the treatment of substance use disorders. Through a series of interactive therapy lessons, the program teaches patients cognitive-behavioral coping skills to resist drug use and to address factors such as craving, depression, and other mood problems and relationship issues that are associated with risk of relapse. The CM component provides concrete rewards contingent on performance of key target behaviors.

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

NIH is supporting the Justice Community Opioid Innovation Network (JCOIN), a collaboration of justice and behavioral health stakeholders that will study approaches to increase high-quality care for people with opioid misuse and opioid use disorder in justice populations. This multi-site clinical research center aims to improve local community public health and safety outcomes for reentering justice- involved individuals who have a history of (or are at risk for) using opioids by comparing two implementation strategies and two interventions at the client and system levels. The study will also examine which implementation strategy is most effective for increasing service linkage and initiation, services retention, and improved opioid-related public health safety outcomes.

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:

Chronic pain affects more than 100 million adults in the United States, resulting in disability, loss of work productivity, and overall reductions in health, making chronic pain a major public health problem with an economic burden estimated at $560–635 billion annually. Opioids, the most frequently prescribed class of drugs to control pain, lack evidence supporting their long-term efficacy and carry a 15% to 26% risk of misuse and abuse among pain patients. Guided imagery (GI) is an effective non-pharmacological intervention for reducing pain, but its effectiveness is limited by patients’ imaging abilities. This project will develop and assess the feasibility of an at-home virtual reality system, Limbix VR Kit, to reduce chronic pain and opioid reliance, as well as improve other functional outcomes, by delivering an immersive GI experience.

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:

Kinoxis has developed a novel small-molecule lead, KNX100, that reduces the severity of opioid withdrawal symptoms in preclinical animal models of opioid use disorder (OUD). KNX100 was discovered from a phenotypic screen of compounds derived from a fragment-based drug discovery program targeting the brain oxytocin system. KNX100 has a favorable pharmacokinetic and safety profile and has undergone testing for efficacy signals in two rodents and two non-human primate species. The proposed activity is to progress the development of KNX100 to treat opioid withdrawal in OUD. The overall objective of the project is to establish the safety and tolerability of KNX100 to enable human efficacy testing to commence in patients requiring treatment for opioid withdrawal. The long-term objective for this development program is to generate human efficacy data to support KNX100 as a potential treatment for opioid withdrawal symptoms and ultimately enable a New Drug Application to the FDA.

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

Very little research has been conducted on better understanding of phenotypic characterization of individuals with OUD (beyond DSM-5 diagnoses) and how these features predict illness severity, treatment retention or outcomes. The primary objective of the deep phenotyping study is to provide a comprehensive phenotypic characterization (e.g., domains of negative affect, reward salience, cognitive control, mental health) of a heterogeneous sample of individuals (n = 1,000) who currently meet one or more DSM-5 diagnostic criteria for OUD and are in treatment for OUD. In a subset of this sample (n = 100), the investigators conduct digital phenotyping to examine the utility of ecological momentary assessment (EMA), digital sensing and social media to predict retention, medication adherence and opioid use outcomes in patients receiving buprenorphine for OUD. It is anticipated that this foundational study will inform the feasibility and utility of such assessments that can be successfully embedded into imminent and future CTN and other OUD clinical trials.

NOFO Title: Medications Development Centers of Excellence Cooperative Program (U54)
NOFO Number: RFA-DA-15-003
Summary:

This U54 Center will use translational research from brain to bedside as a tool for medication development in cocaine use disorder. Preclinical and early phase I clinical PK/PD data will provide information for go/no-go decisions on phase II–III clinical trials with medications that show promise for cocaine use disorder. The overall goal of this research is to create a center that can provide important preclinical and early phase I clinical data to NIDA and pharmaceutical industry partners on novel compounds for cocaine use disorder. The aims related to the theme of the center will be achieved through two cores and three projects: The Administrative Core serves as a general resource for the other projects and the Educational Core, including oversight of fiscal and compliance matters, and will oversee interactions with outside entities, including NIDA and the pharmaceutical industry. The Educational Core will focus on training translational researchers for medication development for addictions across the two institutions.

NOFO Title: The National Drug Abuse Treatment Clinical Trials Network (UG1 Clinical Trial Optional)
NOFO Number: RFA-DA-19-008
Summary:

New Mexico (NM) is an epicenter of the opioid crisis in the United States. Many challenging social determinants, including poverty and unemployment, contribute to high rates of opioid use disorder (OUD) in NM. The aims of the NM node are to (1) develop and maintain a highly efficient platform to conduct clinical trials that will inform evidence-based prevention and treatment of OUD; (2) collaborate on and lead research that addresses and improves outcomes across the OUD Cascade of Care (CoC); and (3) promote uptake of best practices in OUD prevention and care in NM and nationwide through effective dissemination of evidence-based innovations. NM node research will ensure the development of robust and generalizable methods for prevention, identification, and treatment of OUD, including evaluation and modification of the CoC to expand the local and national knowledge base.

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

Migraine is the most common neurological disorder. Currently available treatments fail to effectively manage migraine in most patients. Development of new therapeutics has been slow due in large part to a poor understanding of the underlying pathology of migraine. Endogenous proteases, released in the meninges by resident mast cells, have been proposed as a potential driver of migraine pain via an action on protease activated receptor type 2 (PAR2). The central hypothesis is that PAR2 expression in nociceptors that project to the meninges plays a key role in the pathogenesis of migraine pain. The aims are to: 1) use the established PAR2 development pipeline to design new PAR2 antagonists with improved drug-like properties; 2) use pharmacological tools in a novel mouse migraine model to further understand the potential role of PAR2 in migraine; and 3) use mouse genetics to study the cell type–specific role of PAR2 in migraine pain.

NOFO Title: HEAL Initiative: Early Phase Pain Investigation Clinical Network - Specialized Clinical Centers (U24 Clinical Trials Not Allowed)
NOFO Number: RFA-NS-19-025
Summary:

The Icahn School of Medicine at Mount Sinai (ISMMS) will support the mission of the Early Phase Pain Investigation Clinical Network (EPPIC-Net), through the ISMMS Department of Neurology as the core of a hub and spokes structure. The study contains four specific aims: (1) to streamline and optimize rapid implementation of EPPIC-Net studies, exceeding the required minimum of 100 subjects recruited per year to EPPIC-Net studies; (2) to ensure access to patient populations with a wide range of pain disorders, including CLBP, using a hub and spokes model to ensure effective recruitment; (3) to provide the highest-quality protocol implementation, deep clinical phenotyping of pain disorders, and accurate and complete data collection; and (4) to work collaboratively with the EPPIC-Net Coordinating Centers and investigators from the NIH HEAL Partnership to assist with development/design of clinical trials. The study team will also increase training opportunities through EPPIC-Net within ISMMS and the larger pain research community, training junior investigators to become future pain clinical trials leaders and increase and disseminate knowledge about pain research throughout the network.

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

A persistent problem in the dissemination of medications for opioid use disorder (MOUD) is patient dropout, and matching patients to suitable medication early has the potential to minimize dropout. The overall objective of this secondary data analysis study is to develop and disseminate individual level risk prediction models using harmonized data collected from three multi-site clinical trials from the CTN, in order to predict specific clinical outcomes (e.g., dropout, relapse) for patients treated with MOUD, including methadone, buprenorphine or extended-release depot naltrexone. The relative importance of predictors in the best predictive models will be estimated, which may facilitate refinement of common data elements for future OUD studies. The comprehensive, harmonized database of treatment data created in this study can be used for future secondary data analysis studies and will provide a replicable data pipeline to process and validate OUD data in future protocols.