Funded Projects

NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: PAR-20-092
Summary:

In collaboration with Eolas Therapeutics and the NIH Blueprint Neurotherapeutics Network, AstraZeneca has developed a novel compound for treatment of opioid use disorder, AZD4041, which targets orexin 1 (OX1) receptors in the brain. In animal studies, AZD4041 reduced the motivation to consume opioids or nicotine, reduced relapse-like drug-seeking behaviors, and showed a favorable safety profile. The compound also has proven to be safe in an initial Phase 1 clinical trial in healthy human volunteers. This project will further evaluate the safety (e.g., respiratory depression profile) of AZD4041 in human volunteers, using multiple and increasing doses. Upon successful completion of these studies, the compound will be tested in a proof-of-concept efficacy study in patients with opioid use disorder. If this is successful, the compound will advance to larger Phase 2 and Phase 3 pivotal clinical trial to tests its effectiveness in the treatment of opioid use disorder.

NOFO Title: HEAL Initiative: America’s Startups and Small Businesses Build Technologies to Stop the Opioid Crisis (R43/R44 - Clinical Trial Optional)
NOFO Number: RFA-DA-19-019
Summary:

Opioid use disorder (OUD) can be lethal, with opioid overdose causing more than 115 deaths in the U.S. each day. Although medications are effective at reducing illicit opioid use and overdose deaths, it is well-established that withdrawal and craving are highest in the initial weeks, making this a high-risk period for treatment dropout, relapse, and overdose. Adjunct therapies that can reduce early opioid withdrawal and craving may improve retention in treatment with buprenorphine-naloxone, and recent research has shown that stimulation of a peripheral nerve significantly modulates withdrawal- and craving-related responses for opioids and other drugs. This project will test the effectiveness of the EMPOWER Neuromodulation System, a portable, non-invasive transcutaneous electrical nerve stimulation (TENS) device developed by TheraNova for the treatment of OUD.

NOFO Title: HEALing Communities Study: Developing and Testing an Integrated Approach to Address the Opioid Crisis (Research Sites) (UM1 - Clinical Trial Required)
NOFO Number: RFA-DA-19-016
Summary:

Although there are effective prevention and treatment programs and services to address opioid misuse, opioid use disorder (OUD), and overdose, gaps remain between those needing and those receiving prevention and treatment, in part because of a need to better understand how to make these programs and services most effective at a local level. The National Institutes of Health (NIH) and the Substance Abuse and Mental Health Services Administration (SAMHSA) launched the HEALing Communities Study to generate evidence about how tools for preventing and treating opioid misuse and OUD are most effective at the local level. This multisite implementation research study will test the impact of an integrated set of evidence-based practices across health care, behavioral health, justice, and other community-based settings. The goal of the study is to reduce opioid-related overdose deaths by 40 percent over three years. The Ohio State University is partnering with academic institutions in three other states to study the impact of these efforts in 67 highly affected communities. The study will also look at the effectiveness of coordinated systems of care designed to increase the number of individuals receiving medication to treat OUD, increase the distribution of naloxone, and reduce high-risk opioid prescribing.

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:

There is a compelling need to develop a front line, non-opioid-based acute pain management strategy for outpatient oral surgical procedures. LaunchPad Medical has developed Tetranite® (TN), a novel bone regenerative mineral-organic self-setting adhesive biomaterial. TN has been extensively studied in vivo in a canine jaw model and shown to be effective and well-tolerated. In this project, researchers will demonstrate that drug-loaded TN can be a novel route to providing localized and time release pain medication following wisdom tooth extraction by determining the release profile of various pain medications from TN at different concentrations. The ability to release pain therapeutics in a controlled fashion and directly at the site of injury offers improved pain control following oral surgical procedures without exposing the patient to opioids. This novel approach to pain management can be extended to more invasive orthopedic procedures such as joint replacement, spinal fusions or reconstructive trauma surgery. In Phase II the team will conduct an in vivo study to assess efficacy of medicated TN to address post-operative pain following wisdom tooth odontectomy, optimize incorporation and release of medications in TN formulations, develop cGMP manufacturing process for the compounded product, and ultimately conduct clinical trials for bone void filler using medicated TN.

NOFO Title: Development of Vaccines for the Treatment of Opioid Use Disorder
NOFO Number: BAA-DAIT-75N93019R00009
Summary:

High rates of relapse and overdose deaths pose significant challenges to the treatment of Opioid Use Disorder (OUD). Anti-opioid immunotherapies (i.e., vaccines and monoclonal antibodies) have great potential to reduce long-term opioid use and overdose, with minimal risk of side effects, when used in conjunction with pharmacological treatments and/or behavioral therapies. The ability of an anti-opioid vaccine to induce antibodies that render an opioid less effective, or less rewarding, and protect from accidental overdose could provide an important therapeutic option for patients undergoing treatment for OUD. The goal of this collaborative study is to design, develop, and evaluate vaccines for use in the treatment of opioid use disorder

NOFO Title: HEAL Initiative: Notice of Special Interest (NOSI) regarding the Availability of Administrative Supplements to Support Strategies to Reduce Stigma in Pain Management and Opioid Use Disorder (OUD) and Treatment
NOFO Number: NOT-OD-20-101
Summary:

Medications have proven to be effective for treating opioid use disorder (OUD). Increasing accessibility to buprenorphine provides an opportunity for many with OUD to benefit from its proven effectiveness. Adherence to medication-based treatments however is low, in part because of the stigma associated with use of this and other effective drugs and as such, leads to inadequate treatment and poor outcomes. This study aims to understand the effects of stigma on patient engagement, retention, and outcomes of buprenorphine treatment. Knowledge drawn from the HIV Stigma Theory and tools developed to reduce HIV associated stigma will be used to assess OUD stigma and to develop interventions to reduce it in the context of buprenorphine treatment. The study findings may provide resources to address stigma and thus maximize treatment adherence among those affected by OUD.

NOFO Title: HEAL Initiative: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-22-034
Summary:

Immune checkpoint proteins regulate the immune system to prevent it from indiscriminately attacking cells. Some cancers activate these immune checkpoints to avoid attack, and drugs that target certain immune checkpoints are approved for cancer treatment. The same pathway may also be involved in pain because immune checkpoint proteins, such as programmed death 1 (PD-1) and the molecule that binds to it (programmed death ligand 1 [PD-L1]), also are found in sensory neurons, microglia, and macrophages. This project will investigate PD-1/PD-L1 in different cell populations to determine their contribution to pain and to the effects of opioids such as morphine. This knowledge may help identify new drugs for pain management that modify immune checkpoint activity.

NOFO Title: HEAL Initiative: Sickle Cell Disease Pain Management Trials Utilizing the Pain Management Effectiveness Research Network Cooperative Agreement (UG3/UH3, Clinical Trial Required)
NOFO Number: RFA-AT-23-002
Summary:

Pain is the most common symptom of sickle cell disease (SCD), contributing to poor physical and emotional health outcomes and exacerbating socially determined health disparities at significant societal cost. PRESENCE will be the first study to compare the effectiveness of a cognitive behavioral therapy (CBT) program with and without peer support to usual care as a non-pharmaceutical option for pain management in adolescents and young adults living with SCD. CBT is delivered through an innovative digital app that is accessed on a mobile device with one group receiving self-guided CBT, a second group receiving CBT plus peer support, and a third group receiving usual SCD care. The PRESENCE program is comprised of strong community partnerships that provide the peer support component of the intervention. Measured outcomes will include pain and emotional health.

NOFO Title: PHS 2018-02 Omnibus Solicitation of the NIH for Small Business Technology Transfer Grant Applications (Parent STTR [R41/R42] Clinical Trial Not Allowed)
NOFO Number: PA-18-575
Summary:

One of the current critical needs in addressing the opioid crisis is the development of new overdose-reversal interventions, including wearable technologies that can detect an (impending) overdose from physiological signals to signal for help, or trigger a coupled automated injection of naloxone. This project tests the approach of monitoring respiration by detecting the sounds of breathing in the trachea. This proposal aims to develop a machine learning algorithm that could process those sounds, detect the kinds of patterns of reduced breathing that occur during an opioid overdose, and design a miniature wireless sensor that could be used to detect those sounds. Such a sensor and algorithm could be a key component to a device to detect and intervene in overdoses.

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 be conducted at Emory University School of Medicine in Atlanta, Georgia, allowing access to a diverse population with a high representation of Black/African American women.

NOFO Title: HEAL Initiative: Advancing Health Equity in Pain Management (R61/R33 Clinical Trial Required)
NOFO Number: NS22-002
Summary:

Both pain experience and treatment response are determined by a variety of factors, including race and ethnicity. Inequities in access to healthcare and pain treatment affect patients from minority populations, such as Hispanic/Latino populations of all age groups. This study will develop and test an online intervention—Web-based Tailored Intervention for Preparation of Parents and Children for Outpatient Surgery (L-WebTIPS)—tailored for Latino families of children having outpatient surgeries. The intervention aims to lower child and family anxiety before surgery as well as to reduce post-surgical pain by enhancing parent self-efficacy and behavioral pain coping strategies. After an exploratory phase to assess usability and acceptability of the intervention, the study will evaluate the impact of L-WebTIPS on child pre-surgery anxiety and post-surgery pain as well assess other child and parent outcomes.

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:

Extended-release naltrexone (XR-NTX) reduces overdose risk; however, transitioning to XR-NTX requires detoxification, which is a major hurdle. Non-opioid detoxification with an alpha-2 adrenergic receptor agonist, such as lofexidine, may shorten detoxification time, but it does not reduce the subjective effects of withdrawal. Pregabalin potentiates the activity of glutamic acid decarboxylase, inhibits calcium influx and release of excitatory neurotransmitters, raises GABA levels, and is approved for neuropathic pain, for fibromyalgia, and as an adjunctive therapy for adults with partial onset seizures. The study will test whether pregabalin can be combined with lofexidine to better reduce the subjective effects of opioid withdrawal than lofexidine alone and increase the proportion of patients that transition to XR-NTX. Such a dosing combination could lower the detoxification hurdle for patients who are interested in antagonist treatment or who are in settings where it is unavailable or difficult to access.