Funded Projects

NOFO Title: HEAL Initiative: Tissue Chips to Model Nociception, Addiction, and Overdose (UG3/UH3 Clinical Trial Not Allowed)
NOFO Number: RFA-TR-19-003
Summary:

Researchers will develop multi-organ, microphysiological systems (MPSs) based on human induced pluripotent stem cell-derived midbrain-fated dopamine (DA)/gamma-aminobutyric acid neurons on a three-dimensional platform that incorporates microglia, blood–brain barrier (BBB), and liver metabolism. RNA sequencing and metabolomics analyses will complement the primary DA release measure to identify novel mechanisms contributing to chronic opioid-induced plasticity in DA responsiveness. The chronic pain-relevant aspect of the model will be realized by examination of aversive kappa-mediated opioid effects on DA transmission in addition to commonly abused mu opioid receptor agonists, and by incorporation of inflammatory-mediating microglia. Incorporation of BBB and liver metabolism modules into the microphysiologic system platform will permit screening of drugs. Throughput will be increased by integration of online sensors for online detection of DA and other analytes. Researchers will use a curated set of 100 chemical genomics probes.

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:

Chronic focal neuropathic pain, which includes pain etiologies such as radiculopathy and radiculitis, focal peripheral neuropathies, and low back pain, affects as many as 25 million patients annually in the United States. Chronic focal neuropathic pain is maintained by genome-wide transcription regulation in the dorsal root ganglia (DRG) / spinal cord network. The transcription factors driving this regulation constitute a promising class of targets with the potential to alter the course of pain with a single treatment. DNA decoys are oligonucleotides that specifically inhibit the activity of certain transcription factors. AYX2 binds and inhibits Krüppel-like transcription factors (KLF) in the DRG-spinal cord. The goal of this Phase 1 proposal is to advance AYX2 toward an IND submission, allowing for human clinical trials. We propose in Aim 1 to characterize AYX2 pharmacokinetics in the cerebrospinal fluid and plasma and its distribution in the DRG, spinal cord and brain following an IT injection. With this information, AYX2 will be tested in a panel of complementary toxicology studies in Aim 2 to allow for final IND-enabling studies, supported by Phase 2 of the grant. This research will accelerate development of AYX2 as a novel drug candidate for the non-opioid treatment of pain.

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:

This study will refine and test a collaborative care model for patients with opioid use disorder (OUD) and major depression, post-traumatic stress disorder, or an anxiety disorder in primary care. The primary aims of the study are: (1) prototype and test elements of the research team’s collaborative care models; (2) conduct a randomized study of three collaborative care conditions to determine which is most effective in improving outcomes for people with OUD and mental health conditions: Augmented Usual Care, Collaborative Care, or Collaborative Care + Social Worker; (3) measure clinician and organizational-level factors associated with implementation to increase success; (4) conduct a cost evaluation of each collaborative care model; and (5) work with smaller and rural practices to develop and test effective strategies to manage OUD. Successful completion of this study will provide evidence regarding the elements of integrated collaborative care required to maximize outcomes for individuals with OUD and psychiatric disorders.

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:

Deaths from opioid overdose are highly preventable with early detection and administration of naloxone, but overdose victims often die because they are alone or among untrained or impaired bystanders and thus do not receive timely resuscitation. There is an urgent, unmet need for a low-barrier, easily scalable solution that can identify opioid overdoses in real time and rapidly connect victims to naloxone therapy. This proposal seeks to commercialize an innovative overdose detection software product that can be downloaded on any commodity smartphone and can detect opioid- induced respiratory failure (i.e., overdose) and summon help. The software-only product, SecondChance, converts a smartphone into a short-range active sonar system capable of monitoring breathing and detecting overdose.

NOFO Title: HEAL Initiative: Back Pain Consortium (BACPAC) Research Program Technology Research Sites (UH2/UH3 Clinical Trial Optional)
NOFO Number: RFA-AR-19-028
Summary:

Current diagnostics and treatments of chronic low back pain (cLBP) rely primarily on subjective metrics and do not target all the multidimensional biopsychosocial mechanisms. This multidisciplinary effort will develop and validate a digital health platform and provide meaningful data-driven metrics that enable an integrated approach to clinical evaluation and treatment of cLBP. This platform will facilitate the use of quantitative spinal motion metrics (function), patient-reported outcomes, and patient preference information to enable deep patient phenotyping and inform clinical decision making on personalized treatments in order to improve outcomes. This effort will involve software and hardware development to enable data collection, analysis, and visualization in clinical settings. The outcome of this project will be a digital health platform with data to support regulatory submission for clinical use. At the end of this effort, the researchers will have a validated tool for integration in clinical research studies supported by the BACPAC Consortium.

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: 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: Mechanisms, Models, Measurement, & Management in Pain Research (R01)
NOFO Number: PA-13-118
Summary:

Data suggest that members of minority groups are more likely to develop chronic pain and to have greater pain burden. We will identify a set of promising intervention targets for reducing or eliminating racial/ethnic pain disparities. We will interview adult survivors of serious physical injury, comprised of roughly equal proportions of African-Americans (AA), Latinos, and non-Latino Whites (NLW), and examine their medical records for information on injury severity and medication use in-hospital. Our aims are to determine whether: 1) AA and Latino physical injury survivors experience more severe pain relative to NLW; 2) AA and Latino injury survivors experience greater pain burden relative to NLW counterparts; 3) differences in pain severity burden are linked to a set of target candidates for interventions; and (4) pain outcomes in at-risk minority groups can be linked to a set of target candidates for group-tailored interventions to reduce pain severity and pain burden.

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

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.

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

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:

A more than 5-fold increase in the incidence of neonatal abstinence syndrome has been reported since 2000. Preliminary studies show that prenatal opioid exposure is associated with increased risk of impaired neurodevelopment. Five institutions (Duke University, Arkansas Children’s Research Institute, Cincinnati Children’s Hospital, University of Illinois at Urbana–Champaign, and University of North Carolina at Chapel Hill) have formed a consortium to develop strategies for the Phase II HEALthy Brain and Child Development Study. Research teams will develop instruments and strategies (recruitment/retention protocols, assessment batteries, and novel tools); conduct pilot studies (fetal and postnatal imaging, advanced imaging harmonization and quality control, assessment administration, biosampling) to evaluate instruments; and analyze available data, including imaging, behavioral, cognitive, and maternal data from studies on early brain development, to guide the Phase II study design. Upon completion, the consortium aims to conduct the Phase II study.

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:

Opioids have been significantly over-prescribed and are associated with numerous deaths, resulting in the nation’s current opioid crisis. The FDA recently approved the ?2 adrenergic agonist lofexidine as a non-addictive, non-opioid treatment for opioid use disorder (OUD), but there is a continued, urgent need to develop additional pharmacological alternatives to address both pain and OUD. The psychoactive, natural product, Mitragyna speciosa (kratom), has triggered significant interest in this space because Mitragynine, its main alkaloid, can interact with both mu opioid and ?2 receptors, offering a totally new approach for treating OUD. This project involves the synthesis and research of a series of Mitragynine analogs to better understand the pharmacological mechanisms that underlie Mitragynine’s opioid and adrenergic activities. If successful, this project will result in templates for the design of novel opioid receptor ligands. This advance would greatly improve the knowledge of interactions of these structurally novel compounds with opioid receptors and facilitate the development of these ligands as treatments for OUD.

NOFO Title: HEAL Initiative: Integrated Approach to Pain and Opioid Use in Hemodialysis Patients: The Hemodialysis Opioid Prescription Effort (HOPE) Consortium - Clinical Centers (U01 Clinical Trial Required)
NOFO Number: RFA-DK-18-030
Summary:

For patients with end-stage renal disease treated with long-term hemodialysis (HD), the safety and efficacy of behavioral interventions alone or augmented by safer drugs remain untested. This study will perform a multicenter parallel group randomized controlled trial to test the efficacy of two interventions to reduce opioid use in HD patients. Seven hundred and twenty HD patients with significant and ongoing opioid use will be randomly assigned to (1) telehealth cognitive behavioral therapy (CBT) alone, (2) telehealth CBT augmented by transdermal buprenorphine, and (3) usual care, with follow-up for up to one year. The primary outcome will be prescribed morphine milligram equivalent (MME) over the preceding four weeks. Three patient-reported outcomes (interference by pain, functional status, and quality of life) will comprise the secondary outcomes.