Funded Projects

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: Public Policy Effects on Alcohol-, Marijuana-, and Other Substance-Related Behaviors and Outcomes (R01)
NOFO Number: PA-17-135
Summary:

As states make unprecedented changes to prescription opioid (PO) policies and cannabis laws, the independent and synergistic contributions that both types of measures have on opioid-prescribing practices and opioid overdoses, with and without benzodiazepines (BZDs), are not known. This study will pursue this aim in the U.S. population and Medicaid patients with chronic pain, aiming to: (1) examine whether nonmedical use of POs, BZDs, and heroin and opioid- and BZD-use disorders decreased following enactment of more restrictive PO policies and less restrictive cannabis laws in 2004–2019; and (2) test whether Medicaid patients are less likely to have claims for opioid prescribing, clinic visits for chronic pain, and opioid overdoses following enactment of more restrictive PO policies and less restrictive cannabis laws in 2001–2019. This study will provide findings about the types of policies that are most likely to end the opioid epidemic.

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. Columbia 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: 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

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

Individuals who have been previously incarcerated have a significantly higher risk of dying from opioid overdose, particularly in the first two weeks after release. Providing medication for opioid use disorder (MOUD) to individuals on probation or parole decreases the rate of relapse and recidivism, and increases retention in substance abuse treatment. This study will test a systems-change approach for increasing use of MOUD across a network of seven probation and parole sites to improve linkage to the continuum of evidence-based care for justice-involved individuals. Implementation outcomes include program acceptability, adoption, penetration, sustainability, and costs. Client-level effectiveness outcomes include retention, satisfaction, opioid use, opioid overdoses, recidivism, linkage to OUD treatment, and utilization of recovery services. Targeting the intersection of justice and community-based care has substantial potential for addressing the opioid crisis.

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

The opioid epidemic continues unabated in the United States, and despite the rapid expansion of this crisis, the nature of the risk factors that contribute to opioid misuse remain poorly understood compared with other substances of abuse. The goal of this project is to examine cannabis use and cannabis identification measures as risk factors for opioid misuse while also developing and evaluating novel implicit measures of opioid associations as risk factors for opioid misuse among an at-risk sample of adolescents. Findings from the proposed research are intended to improve the prediction of opioid misuse among adolescents and to potentially identify novel targets for prevention and intervention strategies that aim to combat the opioid epidemic.

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.