Funded Projects

NOFO Title: Grand Opportunity in Medications Development for Substance-Use Disorders (U01 Clinical Trial Optional)
NOFO Number: PAR-18-219
Summary:

There are no FDA-approved medications for stimulant use disorders, and therapies for opioid use disorders remain suboptimal in ways that are now a focus of national attention. Thus, there is a clear need to identify new targets and explore new approaches for addiction medication development. Several lines of evidence suggest that PTPRD (receptor type protein tyrosine phosphatase D) may be a promising target for development of pharmacotherapeutics to treat not only stimulant use disorders but opioid use disorders as well. This research will focus on improving existing PTPRD ligands, identifying their effects on the dopamine and opioid systems, and moving the best novel, patentable PTPRD ligands toward human studies. If successful, this project will generate novel, well-tolerated, and bioavailable PTPRD ligands that display in vitro potency, selectivity and stability, and in vivo modulation of both cocaine and opioid-mediated reward at doses that present no significant toxicity.

NOFO Title: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R21 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-18-042
Summary:

Chronic pain is maintained, in part, by persistent changes in sensory neurons, including a pathological increase in peptides derived from the neurosecretory protein VGF (non-acronymic). Preliminary findings show that the C-terminal VGF peptide, TLQP-62, contributes to spinal cord neuroplasticity and that TLQP-62 immunoneutralization attenuates established mechanical hypersensitivity in a traumatic nerve injury model of neuropathic pain. This project will test the hypothesis that spinal cord TLQP-62 signaling can be targeted for the development of new chronic pain treatments through immunoneutralization and/or receptor inhibition. It will pursue discovery and validation of TLQP-62-based therapeutic interventions along two parallel lines: identification of TLQP-62 receptor(s) and validation of anti-TLQP-62 antibodies as a potential biological therapeutic option for chronic neuropathic pain conditions.

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

Hospital inpatient stays due to opioid-related health problems are a reachable moment for increasing access to treatment with medications for opioid use disorder (MOUD). Hospitalized patients with opioid use disorder (OUD) are at particularly high risk for morbidity, mortality, and high medical costs in the U.S. This study will substantially inform the care management of OUD in hospitalized patients. The project includes a comparative effectiveness research trial and an implementation research trial, which will lead to models of broad dissemination for treatment approaches to this largely unaddressed population. They will examine whether (1) in hospitals with addiction medicine consultation services, hospital-initiated extended-release buprenorphine (XR-BUP), compared with other OUD medications, results in increased engagement in treatment with MOUD following hospital discharge and (2) training hospitals without such consultation services on best practices for initiating MOUD using consultation service hubs improves medication uptake in hospitals and increased MOUD treatment engagement following discharge.

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:

MCAM is a novel opioid antagonist that can be used for opioid overdose reversal and has advantages over naloxone, including a pseudo-irreversible interaction with the ?-opioid receptor and a longer duration of action. Studies in animal models demonstrate MCAM’s long duration of action against the reinforcing and respiratory-depressant effects of remifentanil and heroin, indicating that could be a better treatment option for opioid use disorder. This project studies the pharmacodynamics of MCAM through animal toxicity and safety studies to establish the necessary and sufficient conditions from which to establish MCAM’s safety and antagonist activity in animals and humans. MCAM may be able to prevent all actions of any ?-receptor opioid drug in humans for a longer period of time than any other antagonist given acutely.

NOFO Title: Device-Based Treatments for Substance Use Disorders (UG3/UH3, Clinical Trial Optional)
NOFO Number: PAR-18-494
Summary:

Neurostimulation techniques, such as transcranial direct current stimulation (tDCS), have been used as interventions for substance use disorders. This is a supplement to the currently NIDA-funded UG3 DA047793, “tDCS to Decrease Opioid Relapse,” which will measure behavioral and brain responses following tDCS stimulation delivered during tasks that use a particular brain network involved in cognitive control, and utilizing FMRI to assess the effects. This supplement allows the researchers to add an EEG measurement to the study, to get a complete picture of how tDCS might affect the function of key brain networks in ways that could be helpful for SUDs.

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

There is a significant treatment gap between patients diagnosed with OUD and those who seek treatment, and only a small proportion of those seeking treatment receive MOUD. Primary care is the most common point of health care contact in the U.S. and is an important venue to address stigma, improve access to treatment and improve quality of care. Over the past decade, electronic health record (EHR)-linked Web-based point-of-care clinical decision support (CDS) systems designed to improve quality of chronic disease care have become increasingly sophisticated and successful. A Web-based and EHR-integrated OUD CDS system to offer expert guidance to primary care providers (PCPs) on the diagnosis and management of OUD was developed and piloted. This project will implement the OUD clinical decision support system in three large diverse health care systems and randomize a minimum of 30 clinics to receive the OUD-CDS intervention or usual care (UC). The project will evaluate the impact of OUD CDS on practice process measures and patient outcomes. The study will also prepare for scalability and dissemination by evaluating facilitators and barriers to implementation, determining the costs of implementation and maintenance and assessing the short-term cost impacts of the OUD-CDS.

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

New medication treatment approaches are needed to help address the severe epidemic of opioid use disorder (OUD) and opioid overdose deaths in the U.S. Currently available medications, such as methadone, buprenorphine, and extended release injection naltrexone (XR-NTX; trade name: Vivitrol), are highly efficacious, but their effectiveness in practice is limited by poor adherence, with many patients stopping treatment prematurely and relapsing. The goal of this proposal is to develop an innovative long-acting subcutaneous implanted formulation of naltrexone, the O’Neil Long-Acting Naltrexone Implant (OLANI), toward FDA approval. Expected to produce naltrexone blood levels sufficient to block the effects of opioids for 6 months after implant, OLANI circumvents the need for adherence to monthly injections with XR-NTX and could represent an important new addition to the medical armamentarium for treatment of OUD.

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:

The opioid antagonist naltrexone (NTX) is a proven treatment for opioid use disorder (OUD); however, lack of adherence is a serious limitation that has prevented NTX from reaching its maximum therapeutic potential. To address this limitation, BioCorRx is developing BICX102, a subcutaneous solid depot pellet of NTX, a single implantation of which can provide continual blockade of opioid receptors for up to 3 months. This can prevent patients from being adversely affected by almost any opioid relapse event, while improving efficacy and adherence to behavioral programs that support long-term management and recovery. This proposal comprises the steps required to achieve FDA approval. Successful development of BICX102 would result in a safe and effective 3-month subcutaneous depot pellet/implant containing NTX (1,000 mg) that would be far less reliant on patient compliance.

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:

This study will collaborate with diverse stakeholders to design and conduct a multisite trial evaluating innovative strategies to reduce opioid dosing and improve quality of life and experience with care specific to pain management among adults receiving in-center hemodialysis. A pragmatic parallel arm trial will test the impact of adding a 12-week interactive video cognitive behavioral therapy (IV-CBT) intervention program, compared with CDC guideline-concordant shared decision-making (SDM) for NCCP pharmacotherapy management. The specific aims are to (1) conduct a multisite randomized trial to receive IV-CBT and SDM versus SDM alone over 15 months; (2) investigate and describe barriers and facilitators of the implementation of IV-CBT and also SDM among patients, clinicians, and dialysis staff; and (3) create a collaborative network of investigators and dialysis facilities for efficient recruitment and for dissemination of successful strategies to optimize pain care in dialysis.

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:

The Planning for the HEALthy Early Development Study will contribute to the design and recommended protocol for a future large-scale, multi-site research study to prospectively examine human brain, cognitive, behavioral, social, and emotional development of children beginning prenatally through ages 9–10 and to determine the impact of maternal pre- and postnatal substance use on short- and long-term development of children. The planning study will link investigators across 6 research sites who have complementary experience and expertise in the areas that are essential to designing the study. Planning activities will be accomplished using a coordinated set of 10 working groups. By the end of the planning phase, the 6 consortium sites will have produced and tested a recommended protocol for the future multi-site study and will have established feasibility of carrying out the study protocol at each of the 6 linked sites.

NOFO Title: CTSA Network - Trial Innovation Centers (TICs) (U24)
NOFO Number: RFA-TR-15-002

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

People who use opioids in rural areas suffer worse health and less insurance coverage. The opioid problem in rural areas is of particular concern, as rural areas have higher overdose rates despite equivalent rates of OUD. This is because rural areas have a scant number of clinics and clinicians who provide medication treatment for OUD. Thus, people living in rural areas must travel long distances to access clinics that may or may not have expertise in providing treatment to patients with OUD. Telemedicine (TM) could efficiently increase capacity for delivery of buprenorphine in rural areas and may increase the number of patients receiving medication treatment and improve treatment retention and outcomes. While the development of medication treatments for opioid use disorder (MOUD) capacity in primary care settings with optimal/comprehensive services is desirable, the current opioid crisis with escalating overdose death rates in rural areas suggests a need to implement an efficient, cost-effective system of MOUD services that can be scaled up quickly. The use of a centralized and Medicare-covered TM vendor utilizing a developed methodology and established organizational infrastructure offers the great potential for a rapid rollout to increase access to MOUD and improve treatment retention in rural areas. This cluster randomized clinical trial with two phases will test expanded treatment access to improve retention on MOUD in highly affected rural areas. Phase I will include implementing telemedicine in a limited number of rural sites with varying levels of office-based opioid treatment (OBOT) to inform implementation strategies for the main trial, and Phase II will include evaluate comparative effectiveness between OBOT alone and OBOT + TM at 30 sites.

NOFO Title: HEAL Initiative: Early Phase Pain Investigation Clinical Network - Specialized Clinical Centers (U24 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-19-036
Summary:

EPPIC-Net will provide a robust and readily accessible infrastructure for the rapid implementation and performance of high-quality comprehensive studies of patients with well-defined pain conditions, and the rapid design and performance of high-quality Phase 2 clinical trials to test promising novel therapeutics for pain. Using the Hospital of the University of Pennsylvania as a hub and five additional centers that are part of the UPenn Health System and the Children’s Hospital of Philadelphia (CHOP) as spokes, studies will be conducted as designed by the expertise of the EPPIC Network, which intends to bring intense focus to relatively small numbers of patients with clinically well-defined pain conditions and high unmet therapeutic needs. The UPenn Specialized Clinical Center (SCC) will test novel, efficient study designs including adaptive and platform designs, validation studies of biomarkers, and biomarker-informed proof of principle or target engagement studies in Phase 2 trials of interventions from academic and industry partners.