Funded Projects

NOFO Title: PHS 2016-02 Omnibus Solicitation of the NIH, CDC, FDA, and ACF for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44])
NOFO Number: PA-16-302
Summary:

Since 2002, persons with opioid use disorders who desire medication-assisted treatment can be treated with buprenorphine, which has been shown to be efficacious. Buprenorphine treatment can occur in any medical office-based setting, is prescribed by any physician who seeks to become waivered, and is taken by patients at home unsupervised. However, without visual confirmation of medication ingestion, providers remain unsure if patients divert part or all of their buprenorphine medication. This project will develop the technical and logistical workflow needed to implement a video-­based application, miDOT, for office-­based buprenorphine monitoring during the initial months of care, which will allow health care providers to monitor whether patients ingest the drug and adhere to treatment. The project will configure a video-based DOT platform, evaluate its effectiveness in securing medication ingestion and care retention for illicit opiate users, and solidify routes of sustainable commercial viability with commercial partners.

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:

Deaths from opioid overdose continue to rise; from 2015 to 2016, there was a 28 percent increase in the number of fatal overdoses. Currently available pharmacotherapies include MOR agonists (e.g., buprenorphine) and antagonists (e.g., naloxone), all of which suffer from specific and clear limitations. To address some of the key limitations, Intra-Cellular Therapies Inc (ITI) is developing ITI-333, a novel compound with high-affinity activity at mu opiate (MOP), 5-HT2A, and D1 receptors, that lacks abuse liability and thus offers great promise for the treatment of opioid use disorders. This proposal is for a 2-year UG3 program, including a first-in-human, single ascending dose (SAD) study to assess the safety, tolerability, and pharmacokinetics of ITI-333 in healthy volunteers. This study will then be repeated in a single-center in-patient study with the goal of determining a maximally- tolerated dose (MTD) and completed with human abuse liability and functional pharmacology studies. Together, the researchers believe this clinical development plan will inform further development of ITI-333 and the selection of a cogent Phase 3 clinical path toward FDA approval as a medication for the treatment of OUD.

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.

NOFO Title: Discovery and Validation of Novel Targets for Safe and Effective Pain Treatment (R01 Clinical Trial Not Allowed)
NOFO Number: RFA-NS-18-043
Summary:

Mismanagement of orofacial chronic pain, such as temporomandibular joint and muscle disorders (TMJD) and oral cancer, substantially contributes to opioid overuse; overdose-related deaths; and cardiovascular, renal, and neurological complications at epidemic proportions. The current paradigm implies that orofacial conditions could trigger maladaptation of the immune system and plasticity supporting persistent inflammation, which influences the development and maintenance of orofacial chronic pain. LIGHT (TNFSF14) and Lymphotoxin-beta (LT?), members of the tumor necrosis factor superfamily, provide a balance between protective immunity and immunopathology during chronic inflammatory diseases. This project will test the hypothesis that targeting LIGHT and LT? signaling could prevent the development and inhibit the maintenance of chronic pain produced by TMJD and oral cancer, via peripheral mechanisms involving plasticity of immune, stromal, and tumor cells, as well as sensory neurons. The proposed research is significant as it advances our understanding of mechanisms regulating the development and maintenance of orofacial pain and offers new therapeutic targets and an immunotherapeutic approach for preventing and blocking chronic pain during TMJD and oral cancer.

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

This proposal would address barriers to the NP’s ability to prescribe buprenorphine by incorporating waiver education into NP final semester curriculum. The initial eight hours of training would be provided to students in a face-to-face classroom setting or via live video streaming. The remaining 16 hours would be completed by the NP students through online modules offered by the AANP. Trained NP students would be eligible for one year of peer-to-peer mentorship and inclusion in the MUSC Project ECHO tele-mentoring for new providers. Outcomes to be tracked would be the number of NPs trained who obtain their waiver and the number of individuals treated with MOUD by the NPs trained. Secondary data collected would offer insight into wavier obtainment process and determine need for mentorship for newly waivered providers.

NOFO Title: HEAL Initiative: Effectiveness Trials to Optimize, Implement, Scale, and Sustain the Collaborative Care Model for Individuals with Opioid Use Disorders and Mental Health Conditions (U01 Clinical Trial Required)
NOFO Number: RFA-MH-19-525
Summary:

Some medications for opioid use disorder (MOUD) can be provided in primary care (PC). Systems of team-based PC show promise for improving access and retention in OUD treatment. One such model, collaborative care (CC), includes a care manager, supervised by experts, who help provide evidence-based high-quality OUD care. While CC improves outcomes of depression, other mental health and substance use (MH/SU) disorders and pain, it is unknown how to optimally integrate CC for OUD with other MH/SU disorders. This pragmatic trial tests whether our model of CC for OUD and comorbid conditions increases engagement in MOUD treatment and improves depression symptoms in PC patients with OUD and depression. Innovative pragmatic elements include inclusion of all eligible patients in participating PC clinics, random recruitment and consent, and measurement of main outcomes using only secondary data. These pragmatic elements avoid studying only motivated patients and avoid activating patients randomized to usual care.

NOFO Title: HEAL Initiative: Justice Community Opioid Innovation Network (JCOIN) Clinical Research Centers (UG1 Clinical Trial Optional)
NOFO Number: RFA-DA-19-025
Summary:

A major driver of the U.S. opioid crisis is limited access to effective medications for opioid use disorder (MOUD) that reduce the risk of overdose. Traditionally, jails and prisons in the U.S. do not initiate or maintain MOUD for inmates with OUD prior to their return to the community, which places them at high risk for fatal overdose. The Massachusetts Justice Community Opioid Innovation Network (JCOIN) will study the outcomes and implementation of a 2018 state law that seven county jails must provide all approved forms of medication for OUD. The Chapter 208 initiative has important implications for future policy and practice in the justice and OUD treatment systems at the local, state, and national levels.

NOFO Title: Loyalty and Reward-Based Technologies to Increase Adherence to Substance Use Disorder Pharmacotherapies (R43/R44 - Clinical Trial Optional)
NOFO Number: RFA-DA-19-014
Summary:

Opioid use disorder (OUD) is a key driver of the current opioid epidemic in the United States, but nearly 80% of individuals with OUD do not receive treatment. Buprenorphine medication-assisted treatment (MAT) is an effective form of care for OUD. This project will develop a state-of-the-art, digital therapeutic tool that effectively promotes buprenorphine adherence by providing contingency management rewards and educational content and enables home induction using a new self-monitoring support tool. This tool, named reSET-O+, will be integrated with Pear Therapeutics’ reSET-O, an FDA market-authorized mobile application delivering validated behavioral therapy and intended for use in conjunction with buprenorphine and standard outpatient treatment for OUD.

NOFO Title: NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Required)
NOFO Number: PA-18-344
Summary:

Chronic pain is a significant public health problem associated with tremendous personal and economic burden. First-line treatment consists of opioid medications, but despite only moderate efficacy and unpleasant side effects, rates of opioid prescriptions have quadrupled over the past 15 years, and this has contributed to high rates of misuse, overdose, and mortality. Clearly, alternative, or non-opioid strategies for treating pain are needed. In this context, “opioid-sparing” medications refer to compounds that can be combined with and enhance the analgesic effects of lower-dose opioids without increasing the rewarding properties of either drug. There is preclinical evidence suggesting that cannabidiol (CBD) may have the potential to function as “opioid-sparing” medications, but its ability to alter opioid-mediated analgesia in humans has yet to be determined. This proposal will fill this gap by conducting a double-blind, placebo-controlled, within-subject randomized crossover study of the effects of CBD and morphine co-administration on pain sensitivity and subjective reinforcement on 28 healthy males and females. This is the first known study to investigate the ability of CBD to alter morphine’s analgesic effects in humans. If successful, the model will have a lasting impact on our ability to develop and test medications that reduce our reliance on chronic use of opioid medications for pain relief.

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:

Justice-involved young adults are one of the highest-risk populations for the development of opioid use disorder (OUD) and other significant public health problems, but they usually lack access to evidence-based practices that could potentially prevent this trajectory. The risk of unintentional death and other deleterious outcomes and long-term costs for opioid misuse for young adults, their communities and society (costs estimated at more than $115 billion annually) make this a priority, with rural areas in need of the most attention and assistance. The overriding purpose of the proposed pilot study is to prevent the onset of OUD by improving young adult offenders’ access to evidence-based risk reduction interventions, like contingency management (CM), by testing whether officers in the adult probation and parole setting can deliver such an intervention to their young adult substance using probationers who have not yet developed OUD. The primary motivation for this pilot is the clear public health need for improving and expanding delivery of substance use risk reduction interventions for young adults in the justice system. The ultimate outcome would be prevention of OUD in this high-risk population.

NOFO Number:
Summary:

For many reasons, the emergency department (ED) is a critical venue to initiate opioid use disorder (OUD) interventions. ED patients have a disproportionately high prevalence of substance use disorders and are at an elevated risk of overdose, and many do not access health care elsewhere. Despite this, OUD interventions are rarely initiated in EDs. The Emergency Department Connection to Care with Buprenorphine for Opioid Use Disorder study (CTN-0079) will assess the feasibility, acceptability and impact of introducing clinical protocols for screening for OUD, buprenorphine treatment initiation, and referral for ongoing treatment in ED settings with high need, limited resources and different staffing structures. This extension study will use the existing infrastructure to evaluate the adoption and sustainability of the clinical protocols introduced at each of the study sites and to identify factors influencing their diffusion and effectiveness.

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

Community pharmacies are optimal—yet underutilized—settings for identifying individuals with opioid use disorder (OUD) and increasing their access to treatment. Approximately 93 percent of individuals in the U.S. live within 5 miles of a community pharmacy. The most common opioid-related tool available to pharmacists is the prescription drug monitoring program (PDMP), which provides highly limited information and support for clinical decision making. Appriss Health, the largest U.S. PDMP vendor, covering 42 states, has developed an opioid risk measure, the NarxScore. This study will clinically validate the NarxScore metric and identify high, moderate and low opioid risk thresholds to inform OUD care management within urban and rural community pharmacies. This is a prospective cross-sectional comprehensive OUD risk and behavioral/physical health survey administered electronically with patients (n = 1,523) filling opioid medications in urban/rural community pharmacies in Ohio (pharmacy sites: n = 12) and Indiana (pharmacy sites: n = 3), states that continue to have disproportionately high rates of overdose and opioid prescribing. Correlation, regression and kappa statistics will be calculated for validation; receiver operating curves with sensitivity/specificity values will be employed for threshold identification (with >95 percent power to detect an area of 0.7 under the curve value).