Funded Projects

NOFO Title: Feasibility of Deep Brain Stimulation as a Novel Treatment for Refractory Opioid Use Disorder
NOFO Number: PA-20-272
Summary:

Novel treatments for opioid use disorder are critically needed as the addiction and overdose crises continue. Neuromodulation is a promising supplemental treatment to standard care. The overarching project seeks to evaluate low-intensity focused ultrasound that targets the nucleus accumbens, a primary component of the brain’s reward neurocircuitry. This supplement will expand the number of participants in part of the study and will increase the project’s overall impact consistent with the original objectives and aims of the parent grant.

NOFO Title: HEAL Initiative: Harm Reduction Policies, Practices, and Modes of Delivery for Persons with Substance Use Disorders (R01 Clinical Trial Optional)
NOFO Number: RFA-DA-22-046
Summary:

Harm reduction supplies include fentanyl test strips that allow people who use drugs to identify whether the substance(s) they plan to take contain fentanyl and sterile syringes that help to prevent the spread of infectious diseases among people who inject drugs. One potential way to increase access to harm reduction supplies is mail delivery. This project will describe state-level policies that deter the use of mail-based delivery of harm reduction services, examine characteristics of people who use mail-based harm reduction services, and assess individual preferences related to mail-based harm reduction services.

NOFO Title: Optimization of Non-addictive Therapies [Small Molecules and Biologics] to Treat Pain (UG3/UH3 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-19-010
Summary:

Neuropathic pain is characterized by neuronal hyperexcitability and spontaneous activity, properties associated with activity of hyperpolarization-activated, cyclic nucleotide-regulated (HCN1-4) channels, the source of the pacemaker current, Ih. Inhibition of HCN1-mediated Ih elicits marked antihyperalgesia in multiple animal models of neuropathic pain, including models for direct nerve injury and chemotherapy-induced peripheral neuropathy, and does so with little or no disruption to either normal pain processing or baseline behaviors and activities. The overall objective is to develop a peripherally restricted HCN1 inverse-agonist as a therapeutic for neuropathic pain. Researchers have generated a novel small molecule that combines an antihyperalgesic HCN1 inhibitor with a motif that controls distribution and membrane presentation and is a potential non-opioid antihyperalgesic treatment for peripheral neuropathic pain.

NOFO Title: HEAL Initiative: Sleep and Circadian-Dependent Mechanisms Contributing to Opiate Use Disorder (OUD) and Response to Medication Assisted Treatment (MAT) (U01 Clinical Trial Optional)
NOFO Number: RFA-HL-19-029
Summary:

FDA-approved medications for treating opioid use disorder are effective, but there is a significant unmet need for alternatives, especially relapse prevention. NIDA and the FDA have encouraged investigators to expand the range of therapeutic outcomes, beyond measurement of abstinence. Insomnia is a clinically significant, but understudied, correlate/predictor of relapse to substance use. Yet most medications for treating insomnia have limited efficacy and can produce side effects. The orexin (OX) system plays a key role in sleep and substance use, offering a promising avenue for study. This project will address whether OX-1/2 antagonism is a mechanism that can directly improve outpatient opioid abstinence, or whether OX antagonism corrects sleep deficiencies and indirectly improves opioid abstinence. Specific aims are to determine whether nightly treatment with the OX-1/2 antagonist suvorexant, relative to placebo, 1) increases outpatient opioid abstinence and 2) improves sleep efficiency on the residential detoxification unit. The study will also determine 3) whether improved sleep efficiency predicts greater opioid abstinence (regardless of group assignment).

NOFO Title: Administrative Supplements for Validation of Novel Non-Addictive Pain Targets (Clinical Trials Not Allowed)
NOFO Number: NOT-NS-18-073
Summary:

TWIK-related spinal cord K+ (TRESK) channel is abundantly expressed in all primary afferent neurons (PANs) in trigeminal ganglion (TG) and dorsal root ganglion (DRG), mediating background K+ currents and controlling the excitability of PANs. TRESK mutations cause migraine headache but not body pain in humans, suggesting that TG neurons are more vulnerable to TRESK dysfunctions. TRESK knock out (KO) mice exhibit more robust behavioral responses than wild-type controls in mouse models of trigeminal pain, especially headache. We will investigate the mechanisms through which TRESK dysfunction differentially affects TG and DRG neurons. Based on our preliminary finding that changes of endogenous TRESK activity correlate with changes of the excitability of TG neurons during estrous cycles in female mice, we will examine whether estrogen increases migraine susceptibility in women through inhibition of TRESK activity in TG neurons. We will test the hypothesis that frequent migraine attacks reduce TG TRESK currents.

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:

Though prenatal exposure to opioids and other substances have adverse effects on neurodevelopment, advances in neuroimaging and developmentally sensitive phenotypic measurement now enable characterization of typical and atypical brain-behavior pathways on an unprecedented scale. The Brains Begin Before Birth (B4) Midwest Consortium, a partnership of neuroscience, substance use, perinatal mental health, and child welfare scientists at Washington University School of Medicine (WUSM) and neuroscience, bioethics, pediatric population health, maternal-fetal, and addiction scientists at Northwestern University (NU). This regional consortium will leverage the contrasting approaches of Illinois (punitive) and Missouri (non-punitive) to prenatal opioid use, providing a platform for examining the impact of jurisdictional variations on science and practice. The consortium provide a framework for addressing three major areas of challenge: (1) legal/ethical, (2) recruitment/retention, and (3) imaging/assessment methods.

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:

Current opioid overdose treatment requires administration of naloxone by first responders, which requires timely identification of the overdose, the need for a rescue injection, and immediate availability of the medication. The development of a fail-safe treatment that would provide a life-saving dose of naloxone without the need for intervention by another party could significantly reduce mortality. The researchers aim to develop a new medical device comprising an implantable, closed-loop system that senses the presence of an opioid overdose, automatically administers a life-saving bolus injection of naloxone, and simultaneously alerts first responders.

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: Developing Quantitative Imaging and Other Relevant Biomarkers of Myofascial Tissues for Clinical Pain Management
NOFO Number: RFA-AT-22-003
Summary:

Pain in muscles and surrounding connective tissue (myofascial pain) is a significant health concern affecting hundreds of millions of Americans. There is no objective way to identify and measure myofascial pain. This project will address this unmet challenge by developing a robust approach to identify imaging biomarker(s) that can distinguish different states of myofascial pain. The research will then examine the ability of identified biomarker(s) to predict patient responses to a myofascial pain treatment in a randomized controlled clinical trial.

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: 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 post-traumatic headache (PTH) is highly debilitating, poorly understood, and difficult to treat. This project aims to identify proteins located in the membrane of certain neurons that are critical for the development, maintenance, and/or resolution of PTH. These proteins may be targets for novel treatment approaches that are nonaddictive and have minimal side effects.

NOFO Title: HEAL Initiative: HEALthy Brain and Child Development Study (Collaborative U01- Clinical Trial Not Allowed)
NOFO Number: RFA-DA-21-020
Summary:

The HEALthy Brain and Child Development National Consortium (HBCD-NC) will establish a normative model of developmental trajectories over the first 10 years of life. All sites in the HBCD-NC will carry out a common research protocol and will assemble and distribute a comprehensive research dataset to the scientific community. The HBCD-NC will collect neural, behavioral, physiological, and psychological measures, as well as biospecimens, to characterize neurodevelopmental trajectories. Most participants will be recruited in the second trimester of pregnancy, with a smaller subset recruited at birth, and followed for the first 10 years of life. This study will take place at Washington University in St. Louis, Missouri, and will recruit participants from an urban environment with a high African American population.

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:

Cancer remains a leading cause of death among Hispanic/Latino populations in the United States. Compared with non-Hispanic Whites, Hispanic/Latino cancer patients are more likely to experience poor quality of life and inadequate cancer-related care, including less effective pain relief and poor patient‒provider communication. Additionally, Hispanic/Latino populations often have inadequate access to pain treatment, due to both social disparities and language barriers. However, most behavioral and psychosocial oncology research continues to focus on non-Hispanic Whites, and empirically validated and effective treatment interventions, particularly psychosocial interventions, are often not available in Spanish. This project will generate a Spanish-language version of the painTRAINER internet-based coping skills training program that is both linguistically and culturally sensitive and will evaluate its feasibility and acceptability in Hispanic/Latino patients with persistent cancer-related pain.