Funded Projects

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:

Neonatal Opioid Withdrawal Syndrome (NOWS) affects a growing number of neonates each year due to the ongoing opioid epidemic ravaging the United States. Complex neurobehavioral observation of newborns is the primary modality used. It is subjective and time-consuming by nature, requires significant expertise, and can lead to delays in treatment. The goal of this project is to develop an innovative, low-cost, non-invasive, and easy-to-use brain monitor to objectively assess the severity of withdrawal symptoms in newborns exposed to opioids and provide evidence-based decision support to care providers to improve both short- and long-term developmental outcomes. This device, referred to as NeoGUARD, is based on the continuous, automated, and real-time monitoring of brain function to detect EEG abnormalities shown to be related to NOWS and determine severity to guide pharmacological intervention. This study will focus on the initial prototyping and refinement of the hardware and software, as well as initial evaluations of its use.

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:

While the mu opioid receptor (MOR) antagonist naloxone has proven invaluable as an opioid overdose antidote, naloxone suffers from a very short duration of action (half-life is approximately 1 hour) and has been found to be less effective against newer, long-acting opioids, including fentanyl (half-life is approximately 7–10 hours). This leads to a highly lethal and increasingly prevalent phenomenon known as “renarcotization,” wherein an overdose patient revived with naloxone can re-enter an overdose state from residual fentanyl in the body. Thus, there is a critical need to develop a long-acting MOR antagonist formulation that can address renarcotization by providing multi-hour protection. The goal of this project is to reformulate naloxone using FDA-approved microencapsulation technology into a long-acting injectable (LAI) that can provide 12–24 hours of sustained antagonist activity in vivo. It will employ a proprietary Computational Drug Delivery™ software, called ADSR™, to perform in silico formulation optimization as well as to predict its in vitro dissolution and in vivo pharmacokinetic behavior.

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:

There is a need for an opioid use disorder (OUD) treatment that can prevent relapse in detoxified subjects. Titan's proprietary subdermal implants can provide long-term, non-fluctuating therapeutic levels of drug continuously following a single office-based insertion procedure. The non-biodegradable solid matrix implant formulation virtually eliminates the risk of accidental drug dumping and associated serious toxicity, and its subdermal location assures patient compliance for the 6-month treatment duration. Nalmefene hydrochloride (nalmefene) is an opioid receptor antagonist approved for the management and reversal of opioid overdose. Prototype nalmefene implants inserted subdermally in rats delivered nalmefene continuously for months without any observable safety concerns. This proposed study will develop a 6-month implantable device that delivers nalmefene at a steady rate to prevent relapse to opioid dependence following opioid detoxification. This project will manufacture nalmefene implants, complete nonclinical safety and pharmacology studies, and conduct clinical studies in OUD subjects to support a New Drug Application.

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

The System of Safety (SOS) represents an opportunity to study the implementation of best practice suicide-related care processes that embody the Zero Suicide Essential Elements of Care across emergency departments, inpatient medical and behavioral health units, and primary care clinics associated with a large healthcare system. This effectiveness trial will use a stepped wedge design across a total of 39 clinical units. Aim 1 will measure suicide risk screening and screening's impact on risk identification. Aim 2 will measure the effective implementation of clinician-administered interventions, such as safety planning with means restriction counseling, on suicide, suicide attempts, and suicide-related acute healthcare. Exploratory aims will examine mechanisms of action, moderators, economics, and population effects of the intervention. This study's innovative approach positions it for a significant impact on the fields of suicide prevention, CQI, and effectiveness trial design and analysis.

NOFO Title: The National Drug Abuse Treatment Clinical Trials Network (UG1)
NOFO Number: RFA-DA-15-008
Summary:

Effective treatment for OUD has been shown to improve patient outcomes and reduce health care costs; however, evidence of this effect in primary care settings is severely limited. The health economic findings from this study will supplement the parent PROUD trial’s results regarding clinical effectiveness and implementation outcomes and provide critical contextual information for health systems and other health care stakeholders. The study will evaluate the economic viability of the PROUD collaborative care model for OUD—that is, from the perspective of the health care sector, to what extent do the downstream cost savings associated with improved patient outcomes offset the additional costs of the PROUD intervention? The specific aims are to (1) estimate the start-up and ongoing management costs of the PROUD intervention, (2) assess costs associated with health care utilization for patients who receive primary care treatment in PROUD and usual care clinics and have been identified with recognized OUDs before clinic randomization, and (3) estimate the economic value of the PROUD intervention, measured as net monetary benefit (NMB, incremental benefit minus incremental cost), from the health care sector perspective.

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

Masticatory and spontaneous pain associated with temporomandibular joint disorders (TMJD) is a significant contributor to orofacial pain, and current treatments for TMJD pain are unsatisfactory. Pain-related transient receptor potential (TRP) channels, expressed by trigeminal ganglion (TG) sensory neurons, have been implicated in both acute and chronic pain and represent possible targets for anti-pain strategies. Using bite force metrics, we found TMJ inflammation-induced masticatory pain to be significantly, but not fully, reversed in Trpv4 knockout mice, suggesting the residual pain might be mediated by other pain-TRPs. Our gene expression studies demonstrated that TRPV1 and TRPA1 were up-regulated in the TG in response to TMJ inflammation in a Trpv4-dependent manner. We hypothesize that TRPV1 and TRPA1, like TRPV4, contribute to TMJ pain. Our specific aims will examine the contribution of TRPV1, TRPV4, and TRPA1 to pathogenesis of TMJD pathologic pain including assessment of the role of neurogenic inflammation.

NOFO Title: Clinical Trials or Observational Studies of Behavioral Interventions for Prevention of Opioid Use Disorder or Adjunct to Medication Assisted Treatment-SAMHSA Opioid STR Grants (R21/R33)
NOFO Number: RFA-AT-18-002
Summary:

MAT is the most effective intervention for opioid use disorder (OUD), and methadone maintenance treatment (MMT) is the most commonly prescribed MAT; however, approximately half of people who begin MMT discontinue within a year, and half of people retained in MMT have an opioid relapse within six months. Chronic pain, affecting most people on MMT, could be contributing to relapse in this group. Novel behavioral interventions that address both chronic pain and opioid relapse among people on MAT are needed. Mindfulness Oriented Recovery Enhancement (MORE) was recently developed to treat both pain and opioid misuse. MORE is a group intervention that combines training in mindfulness, cognitive reappraisal, and positive emotion regulation skills to target the dysfunctional cognitive, affective, and behavioral pathways that lead to opioid use relapse. The objective of this proposal is to examine the impact of MORE on opioid relapse and chronic pain among individuals receiving MMT.

NOFO Title: HEAL Initiative: Integrated Approach to Pain and Opioid Use in Hemodialysis Patients: The Hemodialysis Opioid Prescription Effort (HOPE) Consortium - Scientific and Data Research Center (U01 Clinical Trial Required)
NOFO Number: RFA-DK-18-031
Summary:

The University of Pennsylvania Perelman School of Medicine serves as the Scientific and Data Research Center (SDRC) for the Hemodialysis Opioid Prescription Effort (HOPE) Consortium. Specifically, the SDRC will 1) provide scientific leadership for the HOPE Consortium clinical trial; 2) provide comprehensive operational support to the Clinical Centers for implementing the collaboratively designed trial protocol; 3) develop and lead a Stakeholder Engagement Working Group; 4) integrate and analyze data from the electronic health records of the participating Clinical Centers; 5) establish, promote, and maintain consortium-wide high standards for quality assurance and practices; 6) initiate and oversee contracts with industry partners; 7) prepare reports for the Data and Safety Monitoring Board, and support the preparation of Consortium reports of scientific findings; 8) prepare, document, and transfer Consortium data and biosamples to a Central Repository; and 9) develop approaches for disseminating the trial findings to diverse stakeholders.

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 seeks to develop and test a “train-the-trainer” curriculum and training experience that will facilitate the spread and use of the 6BBs by adapting the 6BBs framework and toolkit for health systems and other organizations, training personnel to facilitate its implementation and monitoring results of this implementation.

NOFO Title: HEAL Initiative: Preventing Opioid Use Disorder in Older Adolescents and Young Adults (ages 16–30) (UG3/UH3 Clinical Trial Required
NOFO Number: RFA-DA-19-035
Summary:

Most opioid misuse begins during adolescence and young adulthood. Adolescence is the best time for prevention interventions in settings like school-based health centers (HCs), yet few programs focus on preventing initiation of opioid misuse. This study harnesses the power of video game interventions and incorporates components of effective substance use prevention programs to develop an evidence-informed intervention to prevent the initiation of opioid misuse in adolescents. In partnership with the national School-Based Health Alliance (SBHA), researchers will develop and test a new video game intervention, PlaySmart. It will build on our previous video game intervention that has demonstrated efficacy in improving attitudes and knowledge related to risk behaviors. The study will evaluate the game in a randomized controlled trial (RCT) in 10 school-based HCs and examine strategies for implementing PlaySmart in school-based HCs nationally. This research has considerable potential for wide implementation, reach, and impact on high-risk adolescents through school-based HCs.

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: HEALthy Brain and Child Development Study (HEALthy BCD) (R34 Clinical Trial Not Allowed)
NOFO Number: RFA-DA-19-036
Summary:

This study will determine the feasibility of a multifaceted approach to recruitment of normal and high-risk pregnant women and their children. Three inter-related tasks will support this comprehensive feasibility study. First, an interdisciplinary summit will occur early in the study focused on how best to mitigate risks and maximize benefits to children and families recruited in a future cohort. Second, the feasibility of a multi-faceted recruitment strategy will be assessed. Third, select pregnancy and birth assessments will be collected from recruited participants in this feasibility study while leveraging data across early childhood from existing resources, to inform Phase II study planning. This Phase I of the FL-DECADE study will provide valuable planning and feasibility data to be used for the national efforts to build a large, prospective cohort.

NOFO Title: Advanced Laboratories for Accelerating the Reach and Impact of Treatments for Youth and Adults with Mental Illness (ALACRITY) Research Centers (P50 Clinical Trial Optional)
NOFO Number: PAR-18-701