Funded Projects

NOFO Title: Emergency Awards: HEAL Initiative-Early-Stage Discovery of New Pain and Opioid Use Disorder Targets Within the Understudied Druggable Proteome (R21 Clinical Trial Not Allowed)
NOFO Number: TR22-011
Summary:

High-voltage-gated calcium channels convert electrical signals into physiological responses. After a nerve injury, levels of these channels go down in some neurons in the dorsal root ganglia that communicates pain signals to and from the brain. This decline results in reduced flow of calcium that may underlie pain. This project will develop novel approaches to block these calcium channels p to further study their roles in controlling 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:

This project will examine the association between end plate pathology and chronic low back pain (cLBP) and improve patient selection by developing and translating new imaging tools, technologies, and/or methods (iTTM) that provide accurate, noninvasive measures of end plate pathologies. A search for clinically relevant biomarkers of end plate pathology will focus on novel imaging measures of end plate bone marrow lesion (BML) severity with IDEAL MRI and cartilage endplate (CEP) fibrosis/damage with UTE MRI, assess interactions with paraspinal muscles, and identify metrics that associate with pain, disability, and degeneration. The research will refine imaging and post-processing methodologies by leveraging and expanding existing cross-sectional cohorts and then deploy and validate the new end plate iTTM to other BACPAC sites to test the most promising metrics’ clinical utility. These studies will provide validated iTTM that are useful for addressing the end plates pathology’s role in cLBP, identifying sub-phenotypes, discovering pain mechanisms, uncovering treatment targets, and selecting patients.

NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements. Parent Grant: HEAL Initiative: Non-addictive Analgesic Therapeutics Development [Small Molecules and Biologics] to Treat Pain (UG3/UH3 Clinical Trial Optional)
NOFO Number: Supplement: PA-20-272; Parent NOFO: NS-21-010
Summary:

Negative allosteric modulators (NAMs) of the metabotropic glutamate (mGlu) receptor, mGlu5, have shown promise for treatment of multiple pain conditions without the serious adverse effects and safety concerns associated with opioids. This project will develop and test a novel series of highly selective mGlu5 NAMs that are structurally unrelated to earlier failed compounds and do not form toxic byproducts as with previous mGlu5 NAMs. A lead candidate is now being characterized in several studies to assess readiness for testing in Phase I clinical studies.

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:

As many as 64% of patients with Temporomandibular Joint Disorders (TMJDs) report symptoms consistent with Irritable Bowel Syndrome (IBS). However the underlying connection between these comorbid conditions is unclear and treatment options are poor. As such, pain management for these Chronic Overlapping Pain Conditions (COPCs) is a challenge for physicians and patients. This project will determine whether the convergence of pain from different peripheral tissues and perceived stress occurs in the brain and elicits a change in central neural processing of painful stimuli. This project will identify and validate specific lipids, enzymes and metabolic pathways that change expression in the brain during the transition from acute to chronic overlapping pain that can be therapeutically targeted to treat COPCs. Multi-disciplinary approaches will be used to combine brain imaging, visualization of spatial distribution of molecules, genetics, pharmacological and behavioral research techniques.

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:

Patients with severe, intractable chronic pain primarily receive treatment with opioids, and non-opioid treatment options are urgently needed. These patients may be candidates for treatment using other types of pain medications administered via intrathecal injection—that is, injection directly into the fluid-filled space between the membranes surrounding the brain and spinal cord. Intrathecal injection requires much lower medication doses than systemic administration. Centrexion Therapeutics Corporation seeks to develop CNTX-3100, a highly selective and highly potent novel small molecule that activates the nociception receptor (NOPr), for intrathecal administration using a pump approved by the U.S. Food and Drug Administration. In animal studies, such NOPr agonists had powerful analgesic effects when delivered directly to the spinal cord by intrathecal administration. CNTX-3100 has ideal properties for intrathecal delivery and in animal studies provided pain relief and a safety profile that was superior to intrathecally administered morphine. This project will scale up the drug, develop a formulation that ensures a stable product for intrathecal delivery, and conduct preclinical toxicity studies to prepare for a Phase 1 clinical trial.

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

To avoid the reliance on opioids for treatment of pain, researchers are investigating alternative approaches to disrupt the transmission of pain signals by specialized neurons in the body, such as dorsal root ganglion neurons in the spinal cord. Molecules called voltage-gated sodium channels that are located in the membranes of dorsal root ganglion neurons are essential for transmission of the pain signals. People carrying a specific variant of these channels, NaV1.7, are insensitive to pain; therefore, strategies to block this particular channel might help in the development of non-addictive pain treatment approaches. Navega Therapeutics is developing an innovative gene therapy that specifically targets NaV1.7. Using studies in human cell lines, they will identify the best designs to then test this gene therapy approach in human dorsal root ganglion neurons.

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 emergency department is an ideal venue to reach and intervene with adolescents and young adults at risk for opioid misuse, particularly as young adults may disconnect from primary care when transitioning out of care in pediatric settings. This study will evaluate the efficacy of interventions of varying type and intensity to prevent or reduce opioid misuse or opioid use disorder. The research leverages technology that is appealing to youth to facilitate intervention delivery by health coaches. In this study, adolescents and young adults in the emergency department screening positive for opioid use or misuse will be randomly assigned to one of four intervention conditions with outcomes measured at 4, 8, and 12 months. Technology-driven, scalable interventions delivered via health coaches allow for real-time tailoring to the rapidly changing opioid epidemic, with the potential to prevent an increase in opioid misuse among adolescents and young adults.  Black/African American youth are at increased risk for opioid and other substance use, but they often do not participate in research studies. As a result, it is not known how well prevention interventions work with Black/African American people. This supplement will focus on increasing participant diversity and inclusion by recruiting additional Black/African American participants for this ongoing randomized controlled study of technology-driven prevention interventions.

NOFO Title: Notice of Special Interest to Encourage Eligible NIH HEAL Initiative Awardees to Apply for PA-20-222: Research Supplements to Promote Diversity in Health-Related Research (Admin Supp - Clinical Trial Not Allowed)
NOFO Number: NOT-NS-20-107
Summary:

Social determinants of heath may affect breast cancer diagnosis and disease staging at time of mastectomy. It is unclear if socioeconomic factors such as annual income, marital status/single parent household, number of children, distance from the hospital, and other life stressors facing individuals from under-resourced populations affect development of postmastectomy pain syndrome or response to the drug ketamine. This research will analyze these factors toward mitigating post-mastectomy pain. This analysis will also serve as the basis for further research to define pathways that minimize health disparities plays in the development of chronic, post-surgical pain. The ultimate goal of this research is to normalize risk for chronic pain after breast surgery.

 

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:

Inhaled nitrous oxide, N₂O, is used in emergency departments in Europe to treat pain associated with sickle cell disease as well as for labor, painful fractures, and to manage serious gynecological pain. It is not a viable therapeutic option for home use for reasons such as poor dosing control, potential inhalation equipment issues, and variability in patient ventilation and lung absorption. This project seeks to optimize, characterize, and develop an oral formulation of N₂O that could be used by patients at home for unpredictable and severe episodes of pain associated sickle cell disease. Once developed, the new oral formulation of N₂O will be evaluated to determine whether it or an optimized version is ready for more clinical testing.

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:

The Pain Reduction and Opioid Medication Safety in ESRD (PROMISE) study aims to improve the safety of opioid use and pain management in end-stage renal disease (ESRD) patients on hemodialysis (HD) using a Type I effectiveness-implementation hybrid design. A multisite randomized controlled trial of HD patients from the Hemodialysis Opioid Prescription Effort (HOPE) Consortium will examine the effectiveness of two separate nine-month evidence-based interventions: 1) Opioid Tapering Management (OTM) and 2) Behavioral Pain Management (BPM). We will examine the effectiveness of OTM (versus no OTM, Aim 1) and BPM (versus no BPM) over nine months for reducing opioid use (primary outcome) and improving pain severity (secondary outcome) in HD patients on chronic opioids. The implementation goal will take advantage of the diverse patient, provider, and organizational settings in the HOPE Consortium to evaluate process outcomes.

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:

In this study, 600 to 700 hemodialysis patients receiving chronic opioids will be randomized across the Hemodialysis Opioid Prescription Effort (HOPE) Consortium to enhanced treatment as usual, buprenorphine therapy, or buprenorphine plus mindfulness-based cognitive therapy intervention delivered by telephone and adapted for pain (MBCT-TP). The following specific aims will be assessed: Aim 1—to assess the effectiveness of buprenorphine in reducing chronic opioid use and prescriptions in hemodialysis patients on opioids at baseline, compared with an enhanced treatment as usual intervention and to assess the effectiveness of buprenorphine in improving pain intensity, quality of life measures, and hospitalizations; Aim 2—to assess the incremental effectiveness of MBCT-TP added to buprenorphine compared with buprenorphine alone on pain interference with physical, social, and mental functioning, opioid use, pain intensity, other quality of life measures, hospitalizations, and mortality.

NOFO Title: HEAL Initiative: Advancing Health Equity in Pain and Comorbidities (R61/R33 Clinical Trial Required)
NOFO Number: RFA-NS-22-002
Summary:

Back pain, including low back and neck pain, is one of the most prevalent and disabling pain disorders. Treatment requires ongoing self-management, but most healthcare systems do not support self-care and instead focus on costly, provider-dependent therapies that remain inaccessible to many Black and Hispanic Americans and individuals with less education and income. This project will address these health disparities by developing a personalized self-management treatment program that includes pain education, mindfulness, cognitive behavioral therapy, and exercise – and make it available in community settings.

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:

The proposed SBIR Phase II program seeks to select a first-in-class, peripherally-restricted, and long-acting somatostatin receptor 4 (LA-SSTR4) agonist clinical candidate for development as a novel non-addictive analgesic able to replace opioids for the treatment of moderate-to-severe chronic pain. The program is based on strong scientific evidence showing that activation of peripheral SSTR4 produces broad spectrum analgesic activity and pursues a unique therapeutic strategy.   Unlike opioids, SSTR4 agonists do not induce constipation, respiratory depression, dependence, addiction, or abuse. Finally, unlike SSTR2 and SSTR5, SSTR4 expression in the pituitary and pancreas is very low, supporting that selective SSTR4 agonists are unlikely to perturb peripheral endocrine functions. The preceding SBIR Phase I program has already established the feasibility of conjugating a short-acting, potent, and selective peptide SSTR4 agonist to the antibody carrier. The resulting LA-SSTR4 agonist lead series has high agonist potency and selectivity for SSTR4 and has demonstrated antinociceptive activity in an animal pain model. The proposed SBIR Phase II program seeks to: optimize the existing lead series and select a clinical candidate for development,  validate and prioritize the indication(s) for clinical development using disease-relevant mouse pain models, and characterize the pharmacokinetics and safety/toxicology profile of the clinical candidate in rat and non-human primates to help design subsequent investigational new drug (IND)-enabling studies.