Funded Projects

NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-18-591
Summary:

This project is focused on identifying the clinical, genetic, and neural characteristics that convey risk for prescription opioid addiction. We will leverage the central biorepository and electronic health record (EHR) database of the Geisinger Health System to conduct large-scale genomics research and phenotype development. Through a collaboration with Regeneron Pharmaceuticals, the Geisinger biobank currently contains DNA samples on about 110,000 participants and includes both Illumina OmniExpressExome genotyping and whole exome sequence data, including common and rare variants, from over 60,000 of these subjects. This discovery cohort contains thousands of chronic musculoskeletal pain patients who have been taking greater than 120 mg equivalents of morphine for more than three months. Using EHR and self-report tools to develop a case definition and quantitative scoring, we will derive a clinical/genetic profile of prescription opioid addiction. This profile will be enhanced via integration of neuroimaging data.

NOFO Title: HEAL Initiative: Novel Targets for Opioid Use Disorders and Opioid Overdose (R21 Clinical Trial Not Allowed)
NOFO Number: RFA-DA-22-032
Summary:

Safe and effective options are urgently needed to prevent and treat opioid use disorder and polysubstance use disorders. Previous research in humans and animals suggests that activating the calcium-activated potassium channel KCa2.2 is a promising therapeutic approach for treating substance use disorders and associated health conditions. This project will perform a virtual high-throughput screen using novel machine learning approaches to discover new molecules that interact with the KCa2.2 channel. The newly discovered molecules help develop novel drugs for the treatment of opioid use disorder and associated health conditions.

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:

 Investigating the broader efficacy of sEH inhibition and specifically our IND candidate, EC5026, has indicated that it is efficacious against chemotherapy induced peripheral neuropathy (CIPN). This painful neuropathy develops from chemotherapy treatment, is notoriously difficult to treat, and can lead to discontinuation of life-prolonging cancer treatments. Thus, new therapeutic approaches are urgently needed. The research team will investigate if EC5026 has potential drug-drug interaction with approved chemotherapeutics or alters immune cells function, and assess the effects of sEHI on the lipid metabolome and probe for changes in endoplasmic reticulum stress and axonal outgrowth in neurons. The team proposes to more fully characterize the analgesic potential of our compound and investigate on and off target actions in CIPN models and model systems relevant to cancer therapy.

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; PA-21-071
Summary:

Many molecular gates known as ion channels control the flow of electrical signals to sensory neurons and are thus key mechanisms and targets for understanding and interrupting pain signals. Recent breakthroughs in structural and computational biology shave illuminated specific molecular shapes of ion channels, which permits the improved design and refinement of small, stable protein-like molecules (peptide antigens). These peptides can stimulate an immune response that can then be targeted with a bioengineered antibody to match the peptide antigen. This project will test bioengineered antibodies in a rat model of chemotherapy-induced peripheral neuropathy within a region of the rat spinal cord that transmits signals to and from the brain.

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:

EicOsis is developing a first-in-class analgesic with efficacy against neuropathic pain that will reduce or replace the need for opioids and thus potentially prevent opioid use disorder (OUD). The target of the small molecule inhibitor EC5026 is the soluble epoxide hydrolase, a master regulatory enzyme that modulates the activity of endogenous bioactive lipids. The study will reach the next steps in clinical human clinical trials with EC5026 through additional preclinical studies to expand the efficacy into models of chronic pain conditions. Additionally, detailed pharmacokinetic, metabolism, and distribution studies are proposed that will provide the required information to optimize drug formulation and for advanced clinical trials examining efficacy in humans. EicOsis is meeting current development goals, and EC5026 is well positioned to meet the urgent need of reducing opioid use.

NOFO Title: HEAL Initiative: Novel Targets for Opioid Use Disorders and Opioid Overdose (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-DA-22-031
Summary:

Currently available treatments for opioid use disorder (OUD) are insufficient for many patients. Novel compounds that can promote alterations in brain connections (i.e., neural plasticity) possess enormous potential for improving substance use disorder (SUD) treatments. Psychedelic compounds induce neural plasticity and can elicit long-lasting, beneficial impacts on a wide variety of SUDs. However, these compounds have significant side effects, including hallucinations and cardiotoxicity. Researchers have developed a novel, synthetic derivative of the psychedelic ibogaine, called tabernanthalog, that does not have these side effects. This compound has demonstrated both short- and long-term therapeutic effects in a preclinical model of OUD. This research study will determine the molecular and neural mechanisms through which tabernanthalog affects opioid seeking. It will also evaluate whether the effects are specific to opioids and do not alter response to natural rewards and will examine the efficacy of tabernanthalog in a preclinical model of comorbid opioid and alcohol use disorder.

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: Notice of Special Interest: HEAL Supplements to Improve the Treatment and Management of Common Co-occurring Conditions and Suicide Risk in People Affected by the Opioid Crisis
NOFO Number: NOT-MH-20-025
Summary:

This study will evaluate the implementation of the Zero Suicide framework across six health systems serving over nine million people in collaboration with the Mental Health Research Network. The project will incorporate the voice of the patient and provider stakeholders as part of the implementation of the Zero Suicide framework in three health settings from the NIMH-funded parent award as well as the Southcentral Foundation which is an Alaska Native-owned, nonprofit health care organization serving nearly 65,000 American Indian/Alaskan Native people living in and around Anchorage, Alaska. The team will first systematically engage patients, providers, national consumer advocacy groups, and MHRN scientists in formulating research questions to address the prevention of opioid-related overdoses in people with Opioid Use Disorders (OUD) or people without diagnosed OUD who are using opioids for pain management. Next, the team will utilize semi-structured interviews to determine how people with OUD or people without diagnosed OUD who are using opioids for pain management are experiencing the implementation of the Zero Suicide framework in four diverse health systems. Experiences will be recorded using 80 semi-structured phone interviews in a diverse sample of patients who have survived an opioid-related overdose (50% intentional; 50% unintentional), as well as 20 Addiction Medicine, Primary Care, and/or Specialty Pain Medicine providers.

NOFO Title: HEAL Initiative: Clinical Devices to Treat Pain (UH3 Clinical Trial Optional)
NOFO Number: RFA-NS-19-018
Summary:

Pain is a major problem for spinal cord injury (SCI) patients that tends to persist and even worsen with time. No treatments are currently available to consistently relieve pain in SCI patients. This study will investigate the feasibility of Epidural Electrical Stimulation (EES) using the Abbott Proclaim? SCS system with two electrodes to treat neuropathic pain in patients with thoracic spinal cord injury. In this double-blind, prospective, randomized clinical trial, patients with subacute, traumatic, complete thoracic SCIs with American Spinal Injury Association (ASIA) Impairment Scale A will be randomized to receive either ?EES on? (treatment intervention) or ?EES off? (control intervention) of the target regions for pain control (lead overlying the spinal cord anatomy corresponding with their pain distribution) and neurorestoration (lead overlying the conus medullaris) as an adjunct to physical therapy. This study will help determine whether EES can help patients with SCI neuropathic pain and have more widespread clinical applicability.

NOFO Title: Development of a Device to Objectively Measure Pain (R43/R44)
NOFO Number: RFA-DA-18-012
Summary:

One of the most widely used treatments for chronic pain is opioid analgesics. Importantly, there is evidence of a pathological interaction between opioids and the immune system that can contribute to both opioid tolerance and elevated levels of pain. Chronic pain conditions for which opioids are most often prescribed have been shown to involve dysregulation of the immune system, which may contribute to pathological effects of opioid use in these patients. To address this unmet need, this study aims to develop a reliable, cost-effective, and non-invasive in vitro diagnostic assay for chronic pain with an underlying inflammatory pathology, as a blood test available in primary care settings, with the hope that doctors can use the test to identify which patients might benefit less from opioids and be more likely to become addicted.

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:

A more than 5-fold increase in the incidence of neonatal abstinence syndrome has been reported since 2000. Preliminary studies show that prenatal opioid exposure is associated with increased risk of impaired neurodevelopment. Five institutions (Duke University, Arkansas Children’s Research Institute, Cincinnati Children’s Hospital, University of Illinois at Urbana–Champaign, and University of North Carolina at Chapel Hill) have formed a consortium to develop strategies for the Phase II HEALthy Brain and Child Development Study. Research teams will develop instruments and strategies (recruitment/retention protocols, assessment batteries, and novel tools); conduct pilot studies (fetal and postnatal imaging, advanced imaging harmonization and quality control, assessment administration, biosampling) to evaluate instruments; and analyze available data, including imaging, behavioral, cognitive, and maternal data from studies on early brain development, to guide the Phase II study design. Upon completion, the consortium aims to conduct the Phase II study.

NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-18-591
Summary:

Given the magnitude of the opioid death epidemic, we need multiple approaches to increase use of medication treatment for opioid use disorder (MOUD) for people from diverse geographical locations. Pharmacists as dispensers of and gatekeepers to opioid medications, including those used for OUD treatment, are natural partners of health care providers. Community pharmacists are widely available even in rural areas. This 2-year study will use a mixed-method design that includes qualitative and quantitative approaches to study pharmacists’ knowledge of, attitudes about, and intention to provide patient care and services for screening, brief intervention, and referral to treatment for substance use disorders and MOUD. Study aims are to conduct stakeholder interviews, develop a survey instrument to assess such barriers and facilitators, pilot test the survey instrument, and conduct the survey among licensed pharmacists.

NOFO Title: Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
NOFO Number: PA-18-591
Summary:

The growing opioid use epidemic in the U.S. has been associated with a significant increase in the prevalence of pregnant opioid-dependent women and neonatal abstinence syndrome, which is associated with adverse health effects for the infant and with costly hospitalizations. Maintenance with sublingual (SL) buprenorphine (BUP) is efficacious for opioid use disorder but has disadvantages that may be heightened in pregnant women, including the potential for poor adherence, treatment dropout, and negative maternal/fetal effects associated with daily BUP peak-trough cycles. Extended release (XR) formulations may address some of these disadvantages. The primary objective of CTN-0080 is to evaluate the impact of treating opioid use disorder in pregnant women (n = 300) with BUP-XR, compared to BUP-SL, on maternal-infant outcomes. Other objectives include testing a conceptual model of the mechanisms by which BUP-XR may improve maternal-infant outcomes, relative to BUP-SL; determining the economic value of BUP-XR, compared with BUP-SL, to treat OUD in pregnant women; and evaluating the impact of BUP-XR, relative to BUP-SL, on neurodevelopment when the infant/child is approximately 12 and 24 months of age. Ultimately, this study will help in increasing access to treatment as well as provide quality care for pregnant/postpartum women.