Funded Projects

NOFO Title: NINDS Renewal Awards of SBIR Phase II Grants (Phase IIB) for Pre-Clinical Research (R44)
NOFO Number: PAR-17-480
Summary:

We discovered a class of non-opioid modulators of the T-type Cav3.2 channel that could treat neuropathic pain. In vivo pharmacokinetic and pharmacodynamic studies and preliminary toxicological studies identified AFA-279 and other candidates, which did not produce observable side-effects and showed greater analgesic effects than other neuropathic pain medications in rodent models. The goal of this proposed project is to submit the IND application on our Cav3.2 modulator to the Food and Drug Administration (FDA). We will produce AFA-279 under Good Manufacturing Practice (GMP)–like conditions using chemical manufacturing controls for Good Laboratory Practice (GLP) nonclinical toxicity studies and GMP clinical batch future Phase 1 clinical trials, complete toxicological and safety studies to establish the safety profile of AFA-279, prepare and submit the IND application, and then initiate early clinical trials. Our ultimate goal is to deliver a safer, more effective, non-opioid Cav3.2 channel modulator to patients suffering from neuropathic pain.

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: Notice of Special Interest for HEAL Initiative: Request for Administrative Supplements to Existing Grants for Identification and Validation of New Pain and Opioid Use Disorder Targets within the Understudied Druggable Genome
NOFO Number: NOT-TR-20-008
Summary:

G-protein coupled receptor 3 (GPR3) is an orphan receptor present in the central nervous system (CNS) that plays important role in many normal physiological functions and is involved in a variety of pathological conditions. Although the brain chemical that activates this receptor has not been identified, work with GPR3 knockout mice has identified GPR3 as a novel drug target for several Central Nervous System (CNS) mediated diseases including neuropathic pain. However, despite the emerging behavioral implications of the GPR3 system, little is known about how GPR3 affects behavior due to the lack of potent and selective chemical probes that allow scientists to examine functioning of the receptor. Recently, two cannabinoid chemicals present in the cannabis plant were discovered as affecting GPR3. This study will modify the chemical structure of these compounds to increase their potency and selectivity so that they may be used as pharmacological tools to investigate the role of GPR3 in modulating pain. In addition, this project focuses on identifying new compounds that show promise for development into therapeutics for the treatment of pain.

NOFO Title: HEAL Initiative: Coordinating Center to Support NIDA Preventing Opioid Use Disorder in Older Adolescents and Young Adults (ages 16–30) Initiative (U24 Clinical Trial Not Allowed)
NOFO Number: RFA-DA-19-034
Summary:

The Coordinating Center (CC) will provide centralized logistical support and facilitate communication and coordination of activities across the cooperative. The CC will provide scientific leadership, which will include providing scientific expertise in the areas of implementation research and economic evaluation. The CC will establish an infrastructure for cross-site data collection, management, harmonization, and data sharing and provide expert methodological and statistical consultation.

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 ACT NOW Outcomes of Babies with Opioid Exposure (OBOE) Study – also called the ACT NOW Longitudinal Study – is a longitudinal cohort study to prospectively examine longitudinal outcomes from birth to 2 years of age among infants who were exposed to opioids in utero as compared to matched controls. The objectives of this study are to i) determine the impact of pre-birth opioid exposure on brain structure and connectivity over the first 2 years of life, ii) define medical, developmental, and behavioral outcomes over the first 2 years of life in infants exposed to opioids, and iii) Explore whether and how the home environment, maternal mental health, and parenting affect brain connectivity and neurodevelopment trajectories over the first 2 years of life. This research will use an innovative approach to engage a more diverse study population and thereby improve the generalizability of the research findings.

NOFO Title: Data Coordinating Center for the NICHD Neonatal Research Network (U24)
NOFO Number: RFA-HD-18-010
Summary:

The ACT NOW Eat, Sleep, Console (ESC) Clinical Trial approach to the management of neonatal opioid withdrawal syndrome (NOWS) emphasizes parental involvement, simplifies the assessment of infants with NOWS and focuses interventions on non-pharmacologic therapies. Although outcomes following implementation of the ESC care approach, inclusive of the ESC Care Tool, appear promising and initial accounts suggest that it is safe, there has yet to be a rigorous randomized clinical trial to demonstrate the safety, efficacy and generalizability of its use in the care of infants with NOWS. The ESC Clinical Trial leverages the infrastructure and collaborations of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network and the IDeA States Pediatric Clinical Trials Network to reach the populations most affected by the opioid epidemic. The trial will provide answers to numerous critical gaps in our knowledge with respect to the best practices for the identification and management of infants with NOWS, as well as our understanding of the outcomes of these infants.

NOFO Title: HEAL Initiative: Research to Foster an Opioid Use Disorder Treatment System Patients Can Count On (RM1 - Clinical Trial Optional)
NOFO Number: RFA-DA-23-046
Summary:

Although medication-based treatment for opioid use disorder can effectively reduce overdose risk and improve health outcomes, most people discontinue treatment too soon. Quality measures that inform opioid treatment programs about how many patients remain in treatment relative to peer programs could motivate those programs to pursue quality improvement activities, such as helping patients navigate logistical barriers to receiving treatment. This project will test approaches to developing and disseminating retention and outcome measures for opioid treatment programs.

NOFO Title: HEAL Initiative: Data Coordinating Center for the Neonatal Opioid Withdrawal Syndrome Pharmacological Treatments Comparative Effectiveness Trial (U24 Clinical Trial Required)
NOFO Number: RFA-HD-21-032
Summary:

Neonatal Opioid Withdrawal Syndrome (NOWS) is a condition that occurs when newborns are exposed to opioids during pregnancy. Symptoms often include tremors, excessive crying, sleep deprivation, and swallowing difficulties. Cases are rising, with a newborn affected by NOWS approximately every 15 minutes. Currently, healthcare providers in the United States lack standard, evidence-based treatments for NOWS. 

This project is part of a multi-center, randomized controlled clinical trial that directly compares NOWS treatments—morphine, methadone, and buprenorphine—and takes into account other types of non-drug therapies, such as behavioral interventions. The goal is to generate results that can inform clinical practice guidelines and give newborns with NOWS the best start possible. 

This site will serve as the Data Coordinating Center for the clinical trial to provide high-quality and impartial biostatistical expertise for all the study sites.

NOFO Title: HEAL Initiative: Harm Reduction Policies, Practices, and Modes of Delivery for Persons with Substance Use Disorders: Coordination Center (R24 Clinical Trial Optional)
NOFO Number: RFA-DA-22-042
Summary:

This project creates the HEAL Harm Reduction Network Coordination Center, which will provide support to the nine research studies in the HEAL Harm Research Reduction Network. The center will provide administrative and logistical help; support data harmonization and data sharing; involve stakeholders in all network activities; and share research findings and other products with researchers, practitioners, stakeholders, and the general public. 

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: Discovery and Functional Evaluation of Human Pain-associated Genes and Cells (U19 Clinical Trial Not Allowed)
NOFO Number: NS22-018
Summary:

This project will identify molecular characteristics of human sensory neurons and non-neuronal cells from the human dorsal root ganglia. This structure located outside the spinal cord is integrally involved in communicating pain signals to and from the brain. The research will use molecular approaches to characterize tissues obtained from organ donors and in patients who experience chronic pain. The findings will also help generate a connectivity map, or “connectome,” of nerve cell connections between the dorsal root ganglia of the spinal cord and the brain.

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

Chronic pain diminishes the quality of life for millions of patients, and new drugs that have better efficacy and/or fewer side effects are needed. A promising target is the sphingosine-1-phosphate (S1P) receptor system, which mediates central nervous system (CNS) neuromodulatory functions. FTY720-phosphate, the active metabolite of FTY720 (FTY), acts as an agonist at four of the five S1P receptors (S1P1, 3, 4, 5). We propose that the S1P1 receptor is a target for treatment of neuropathic pain. We will test whether S1P1 receptors mediate anti-hyperalgesic effects in a mouse neuropathic pain model. The specific aims are to: 1) determine the role of S1P1Rs in alleviation of neuropathic pain by S1PR ligands; 2) determine the role of FTY-induced S1PR adaptation in FTY-mediated reversal of neuropathic pain; and 3) determine the role of S1P and S1P1 receptors in spinal glia in CCI-induced neuropathic pain and its reversal by FTY.