Funded Projects

NOFO Title: Notice of Special Interest (NOSI): Encourage Eligible NIH HEAL Initiative Awardees to Apply for Administrative Supplements to Support Career Enhancement Related to Clinical Research on Pain
NOFO Number: NOT-NS-22-087
Summary:

This project supports a post-doctoral trainee to develop the skills and knowledge needed to pursue a career in clinical pain research. The research will involve optimizing a GetActive mind-body activity program to overcome barriers that prevent disadvantaged older adult populations in community health clinics from access to non-pharmacological pain management strategies. The research will include qualitative analysis of secondary data, a literature review to evaluate methods, and feasibility for establishing a community advisory board for the GetActive project.

NOFO Title: Notice of Special Interest (NOSI): HEAL Initiative: Biospecimen Collection in Pregnancy
NOFO Number: NOT-DA-23-005
Summary:

Opioid use during pregnancy is associated with adverse outcomes for pregnant individuals and offspring. The mechanisms through which these outcomes arise and the consequences of prenatal opioid exposure on child health and development remain largely unexplored. The HEALthy Brain and Child Development (HBCD) Study is a nationwide longitudinal prospective study of early child development that will assess a broad spectrum of biological, behavioral, social, and health factors among 7,500 pregnant women and their children from pregnancy to mid-childhood. This supplement will expand the biospecimen collection of the HBCD protocol at the University of North Carolina at Chapel Hill to include delivery specimens (placenta, cord tissue, and cord blood). This will provide an unprecedented resource-generating opportunity for the larger scientific community to comprehensively evaluate mechanisms that mediate the connection between substance use during pregnancy and adverse neonatal, infant, and/or maternal health outcomes and inform innovative preventive strategies.

NOFO Title: HEAL Initiative: Planning Studies for Initial Analgesic Development [Small Molecules and Biologics] (R61 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-21-029
Summary:

Common chronic pain syndromes such as fibromyalgia, temporomandibular disorder, and low back pain, are significant health conditions for which safe and effective treatments are needed. Previous studies have identified the adrenergic receptor beta-3 (Adrb3) as a novel target for chronic pain, but past attempts to block this receptor have not worked. This project aims to identify and develop new molecules to attach selectively and block Adrb3 without entering the brain and spinal cord. The research will test these molecules in rodent animal models to determine their ability to block pain without significant side effects.

NOFO Title: HEAL Initiative: Translational Development of Diagnostic and Therapeutic Devices (R18 Clinical Trial Not Allowed)
NOFO Number: RFA-EB-22-002
Summary:

Infants exposed to opioids during pregnancy can develop neonatal opioid withdrawal syndrome (NOWS). To date, clinicians generally use subjective evaluation to determine if an infant has NOWS, how severe the condition is, and if the infant needs treatment with or without medications. This project will evaluate whether an objective physiologic measure—continuous measurement of oxygen levels in the infant’s blood—can be used to develop a scoring system for assessing NOWS severity. The project will also develop and test a device to continuously monitor blood oxygen levels in the infants.

NOFO Title: Advancing Validated Drug Targets for Substance Use Disorders (R43/R44 - Clinical Trial Not Allowed)
NOFO Number: RFA-DA-22-023
Summary:

New and safe therapeutic targets for treating opioid use disorder are needed. One promising approach is to test drugs currently approved by the U.S. Food and Drug Administration that work independently of the body’s opioid system. The medication memantine targets N-methyl-D-aspartate (NMDA) receptors in the brain, which have been implicated in the development and maintenance of addiction. This project will study a miniature version of multiple memantine molecules bound together that attaches only to NMDA receptors that are not within nerve connections. The research will evaluate the safety, misuse potential, and effectiveness of this molecular assembly in preclinical models. 

NOFO Title: Development and Validation of Pain-Related Models and Endpoints to Facilitate Non-Addictive Analgesic Discovery
NOFO Number: NOT-NS-22-095
Summary:

Effective development of non-addictive therapies for pain requires animal models that reflect the human condition. Unfortunately, currently used models have limitations and have not always done a good job of predicting what will work in human patients. This project will refine a new way of measuring pain-related behaviors in mice that takes advantage of more natural mouse behavior and is less influenced by experimenter biases and artifacts. The research will verify that the promising results hold up in several different types of pain and that different classes of clinically used pain medications are effective. They will also make sure the data can be reproduced by an outside laboratory. If successful, this will support the use of this new read-out for future pain therapy development.

NOFO Title: HEAL Initiative: Opioid Exposure and Effects on Placenta Function, Brain Development, and Neurodevelopmental Outcomes (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-HD-23-030
Summary:

This project will study the harmful effects of illicit and prescription opioid use during pregnancy and its consequences on the mother, fetus, and placenta. The research will integrate multiple different technologies to study molecular changes in biospecimens taken from research participants. Samples to be collected at birth and characterized include plasma and urine from the mother across the three trimesters of pregnancy, tissue samples of the placenta, and fetal cord blood. This research aims to shed new light on the underlying biology of opioid exposure on the placenta during pregnancy toward development of early interventions during opioid-exposed pregnancies. 

NOFO Title: HEAL Initiative: HEAL Data2Action – Innovation and Acceleration Projects, Phased Awards (R61/R33, Clinical Trial Optional)
NOFO Number: RFA-DA-23-057
Summary:

Older adults make up more than half of all surgical patients in the United States, putting them at risk for a range of harmful outcomes including misusing opioids, developing opioid use disorder (OUD), opioid overdose, and surgical complications. This project seeks to understand whether pre-surgery interventions can prevent harmful opioid-related outcomes. The research will combine data from a registry of electronic health records and from Medicare claims data to learn about the relationship between these interventions and opioid-related outcomes including persistent opioid use, OUD, and other harmful outcomes.

NOFO Title: HEAL INITIATIVE: Development of Therapies and Technologies Directed at Enhanced Pain Management (R43/R44 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-23-006
Summary:

Every year, more than 330,000 Americans are hospitalized for hip fractures. Rapid surgical intervention and pain treatment is critical to recover mobility and reduce other health complications. Ultrasound-guided regional anesthesia techniques are an effective alternative to opioid medication, but require specialized training for use in the emergency department. This project will develop and validate an easy-to-use ultrasound-based regional anesthesia guidance system, to ultimately improve access to non-opioid-pain treatment for hip fracture pain.

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: RFA-TR-22-011
Summary:

Chronic pain results in long-term changes throughout the central nervous system. These include abnormal structure and function of the frontal cortex region of the brain, which relays pain messages and also the common pain-related conditions depression, anxiety, and cognitive impairment. Peripheral nerve injury results in widespread and long-lasting changes to DNA in the frontal cortex. DNA methylation, in which chemical tags are attached to DNA, is one way the body controls the activity of genes over time. This control occurs via proteins that recognize tagged DNA, and some of these proteins do not work properly in the frontal cortex many months after nerve injury. These changes occur after nerve injury and are linked to mechanical sensitivity. This project will determine this DNA-binding protein is a good target for finding new medications for chronic pain. 

NOFO Title: HEAL Initiative: Multilevel Interventions to Reduce Harm and Improve Quality of Life for Patients on Long Term Opioid Therapy (MIRHIQL): Resource Center (U24- Clinical Trial Optional)
NOFO Number: RFA-DA-23-042
Summary:

Decreasing opioid dosing faster than advised by clinical recommendations often leaves chronic pain unaddressed and may increase the risk of overdose and suicide compared to continuing long-term opioid treatment. Clinical and research communities are uncertain about how to assess and manage long-term opioid therapy, despite having diagnostic and treatment frameworks for chronic pain and opioid use disorder. Because of this undefined space, health policy, institutions, and practitioners lack clear advice on long-term opioid prescribing in chronic pain. The goal of the MRC is to provide infrastructure support for the network; create a risk-benefit decision tool to assist providers in determining when opioids should be continued as prescribed, tapered, or tapered/discontinued; and develop and validate a clinical definition for this population (name, identifying associated symptoms/behaviors, and generating a screening tool). This project will leverage big data analytics in administrative datasets, natural language processing approaches in electronic health records, and cohort modeling techniques to accomplish these key responsibilities. These efforts will complement the qualitative data collection approaches in the Becker Resource Center. 

NOFO Title: HEAL Initiative: Opioid Exposure and Effects on Placenta Function, Brain Development, and Neurodevelopmental Outcomes (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-HD-23-033
Summary:

Exposure to prescription opioids during pregnancy can alter growth of the fetus and cause persistent neurological problems during childhood. This project will identify biological underpinnings of oxycodone exposure on health of the placenta, brain development of the fetus, and behavioral problems observed in early infancy. This research will also assess whether melatonin supplementation can limit these harmful outcomes. Overall, the research aims to characterize the health effects of oxycodone used during pregnancy, as well as to point to new tools and molecular indicators (biomarkers) for diagnosing, treating, and preventing opioid harm to the fetus and mother.

NOFO Title: Development of Medications to Prevent and Treat Opioid and/or Stimulant Use Disorders and Overdose (UG3/UH3 - Clinical Trial Optional)
NOFO Number: PAR-22-200
Summary:

There is an urgent need for improved medications to treat OUD. This project will test cebranopadol, a novel synthetic medication that interacts in a new way with the human opioid system as a safe and potentially effective alternative treatment for OUD. The research will test the safety and efficacy of cebranopadol in preclinical and clinical studies, toward guiding future research to support potential approval of this medication by the U.S. Food and Drug Administration.