Funded Projects

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:

A main goal of the NIH HEAL Initiative and the Early Phase Pain Intervention Clinical Network (EPPIC-Net) is to improve non-opioid pain management. This award will leverage the resources at one of EPPIC-Net’s Specialized Clinical Centers by implementing and evaluating strategies to improve the engagement, recruitment, and retention of individuals from underserved racial/ethnic minority populations to participate in EPPIC-Net clinical trials. Since environmental, cultural, and genetic factors may account for observed differences in pain responses between racial and ethnic groups, enrollment of a diverse sample in pain research is crucial to obtain a complete understanding of the effectiveness of any proposed pain therapeutic intervention. The success of these activities will be evaluated, and a toolkit will be created to define best practices that can be by other EPPIC-Net sites and additional trials.

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:

Managing persistent pain has long been a difficult challenge, one that is heightened by the recent opioid crisis. Although many potential solutions may exist, demonstrating their efficacy in a multicenter trial is a considerable obstacle. There is broad consensus that a nationwide clinical research network is necessary to promote innovation. A hub-spoke complex of academic medical centers with considerable experience in pain management clinical trials and biomarker validation will leverage existing resources to make clinical trial execution efficient and rapid. Together, spokes will provide maximum flexibility, ready to accommodate studies in any well-characterized pain condition.

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:

 Quell Therapeutics uses the Optopatch platform for making all-optical electrophysiology measurements in neurons at a throughput sufficient for phenotypic screening. Using engineered optogenetic proteins, blue and red light can be used to stimulate and record neuronal activity, respectively. Custom microscopes enable electrophysiology recordings from 100’s of individual neurons in parallel with high sensitivity and temporal resolution, a capability currently not available with any other platform screening technology. Here, researchers combine the Optopatch platform with an in vitro model of chronic pain, where dorsal root ganglion (DRG) sensory neurons are bathed in a mixture of inflammatory mediators found in the joints of osteoarthritis patients. The neurons treated with the inflammatory mixture become hyperexcitable, mimicking the anticipated cellular pain response. Investigators calculate the functional phenotype of arthritis pain, which captures the difference in action potential shape and firing rate in response to diverse stimuli. The team will screen for small molecule compounds that reverse the pain phenotype while minimizing perturbation of neuronal behavior orthogonal to the pain phenotype, the in vitro “side effects.” The highest ranking compounds will be chemically optimized and their pharmacokinetic, drug metabolism, and in vivo efficacy will be characterized. The goal is to advance therapeutic discovery for pain, which may ultimately help relieve the US opioid crisis.

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 University of California, San Francisco, as part of the Back Pain Consortium (BACPAC) Research Program, has established a Core Center for Patient-centric Mechanistic Phenotyping in Chronic Low Back Pain (REACH). The main goal of REACH is to define different subtypes (phenotypes) of chronic low back pain as well as to identify underlying pain mechanisms that can lead to effective, personalized treatments for patients across all population subgroups. To achieve this goal, REACH is, or will be, participating in several clinical trials, and it is imperative that the patients participating in these trials reflect the diversity of the U.S. population. Therefore, this project seeks to adapt methods that have successfully improved minority participation in other settings as well as to develop and deploy digital strategies that can promote recruitment and engagement of patients from marginalized populations.

NOFO Title: HEAL Initiative: Non-addictive Analgesic Therapeutics Development [Small Molecules and Biologics] to Treat Pain (UG3/UH3 Clinical Trial Optional)
NOFO Number: RFA-NS-21-010
Summary:

Overreliance on opioids to treat chronic pain has been a contributor to the increase in individuals experiencing opioid addiction. This project aims to develop an innovative treatment approach for chronic pain that targets the cannabinoid receptor 1 (CB1R) to block the sensation of pain. The approach seeks to identify molecules that interact with a different part of the CBR1 receptor than do endocannabinoids and the primary active component of cannabis, tetrahydrocannabinol. Molecules that bind to and activate CBR1 in this different way (at an “allosteric” site) may produce nerve signaling that might differ from the effects of cannabis and endocannabinoids. This redirection of signaling pathways could help eliminate the risk of adverse effects observed with natural cannabinoids and other CBR1-binding molecules. The goal of this project is to identify a CB1R allosteric molecule, conduct studies toward obtaining federal permission to develop it as a medication, and to test it in a Phase I clinical study.

NOFO Title: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-18-043
Summary:

Validation of novel pain targets is a critical step toward the development of new non-addictive therapeutic agents for chronic pain management. Recent findings suggest that nerve injury-induced concurrent upregulation of the calcium channel alpha-2delta-1 subunit (CaValpha-2-delta-1) and thrombospondin-4 (TSP4) proteins in sensory and spinal cord neurons contributes to neuropathic pain development. Specifically, induction of aberrant excitatory synapse formation and sensitization of neurotransmission in spinal cord underlies this process; accordingly, a target site has been identified in the TSP4 that plays a critical role in mediating these pathological changes upon interaction with the CaValpha-2-delta-1 protein. This project will validate this novel target site in TSP4 for development of non-addictive pain medications, utilizing multidisciplinary approaches to investigate if blocking and genetic deletion of the target site can block or prevent the development of chronic pain state, aberrant excitatory synapse formation, and spinal cord neuron sensitization after injury in multiple rodent neuropathic pain models.

NOFO Title: Discovery of Biomarkers, Biomarker Signatures, and Endpoints for Pain (R61/R33 Clinical Trial Optional)
NOFO Number: RFA-NS-18-041
Summary:

Multidisciplinary chronic pain treatments show incomplete recovery at the population level because of significant heterogeneity on the individual level in the high impact chronic pain population. Subgroups of individuals either completely respond, do not change, or even worsen following pain management. Therefore, diagnostic biomarker signatures are needed to differentiate high impact chronic pain from low impact chronic pain. This study aims to develop prognostic biomarkers to predict the disease trajectory for individuals with musculoskeletal high-impact chronic pain. These biomarker signatures will integrate central nervous system (CNS), multi-?omic?, sensory, functional, psychosocial, and demographic domains into detection algorithms. Biomarker signatures from the proposed research are intended to facilitate risk and treatment stratification for clinical trial design and to facilitate treatment decisions in clinical practice for patients with musculoskeletal chronic pain.

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:

Despite the significance of spine disorders, there are few reliable methods to determine appropriate patient care and evaluate intervention effectiveness. The research and tool development take the critical next step in the clinical translation of faster, quantitative magnetic resonance imaging (MR) of patients with lower back pain. The multidisciplinary Technology Research Site (Tech Site) of BACPAC will develop Phase IV (i.e., technology optimization) technologies and/or methods (TTMs) to leverage two key technical advancements: development of machine learning-based, faster MR acquisition methods and machine learning for image segmentation and extraction of objective disease related features from images. The team will develop, validate, and deploy end-to-end deep learning-based technologies (TTMs) for accelerated image reconstruction, tissue segmentation, and detection of spinal degeneration to facilitate automated, robust assessment of structure-function relationships between spine characteristics, neurocognitive pain response, and patient-reported outcomes.

NOFO Title: Research Supplements to Promote Diversity in Health-Related Research (Admin Supp - Clinical Trial Not Allowed)
NOFO Number: PA-20-222
Summary:

Despite the significance of spine disorders, there are few reliable methods to determine appropriate patient care and evaluate intervention effectiveness. The Back Pain Consortium Research Program
(BACPAC) is developing machine learning-based methods to obtain disease-related features from biological images. This project supports a scientist from a group underrepresented in biomedicine to expand ongoing research to improve ways to interpret medical data about spine disorders and associated pain.

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:

There is an urgent need for new non-opioid therapeutic agents that treat the pain associated with Osteoarthritis (OA) ? a chronic, progressive disease that leads to pain in weightbearing joints, pain during movement, and pain at rest. This project will refine techniques for targeting several proteins expressed in sensory neurons associated with OA pain, with the goal of testing the potential of these proteins to serve as targets for development of effective, non-opioid painkillers.

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: Notice of Special Interest to Encourage Eligible NIH HEAL Initiative Awardees to Apply for Administrative Supplements to Support Career Enhancement Related to Clinical Research on Pain (Admin Supp – Clinical Trial Not Allowed)
NOFO Number: NOT-NS-21-048
Summary:

Improving pain treatment for is a major goal of the NIH HEAL Initiative. This award supports an early career physician toward achieving a future in clinical pain research and in conducting phase II clinical trials focused on pain. Research activities will provide this individual with the skills needed to serve as a primary investigator for future clinical trials in chronic pain and will help to answer a key question that could improve the design of analgesic clinical trials for neurogenic intermittent claudication, a distinct form of chronic low back pain for which no available treatment exists.

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.