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:

A recent FDA public meeting identified sleep disturbance as a primary contributor to opioid use disorder (OUD) treatment failure. Suvorexant (SUVO; Belsomra®) is a dual orexin receptor antagonist that is FDA-approved for insomnia, with low addiction liability, that improves sleep continuity with a single dose, has an extremely safe and mild side-effect profile, has clear interactions with the opioid system, and has not yet been evaluated in OUD patients. The hypothesis is that SUVO will improve total sleep time during withdrawal, have no addiction liability, and be more efficacious than trazodone, a common OUD-associated insomnia medication. Primary outcomes will be objective sleep measures and addiction liability. Secondary measures will include objective, biological, and self-report measures of opioid withdrawal severity, treatment retention, craving, and stress. Results will advance the treatment of OUD, the understanding of sleep and opioids, and the use of SUVO in clinical populations.

NOFO Title: HEAL Initiative: Justice Community Opioid Innovation Network (JCOIN) Methodology and Advanced Analytics Resource Center (U2C Clinical Trial Not Allowed)
NOFO Number: RFA-DA-19-023
Summary:

Many individuals with opioid use disorder (OUD) pass through the criminal justice system over the course of their life. Improved access to high-quality, evidence-based addiction treatment in justice settings will be critical to addressing the opioid crisis. Through the Justice Community Opioid Innovation Network (JCOIN), the National Institutes of Health will study approaches to increase high-quality care for people with opioid misuse and OUD in justice populations. The Methodology and Advanced Analytics Resource Center (MAARC) will provide data infrastructure support across the network using advanced methods that provide best-in-class data storage, management and security with added value to clinical trials through products of forecasting, rapid real-time assessments, explication and exploration of trial findings, and cost-effectiveness analysis.

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 and well curated research dataset to the scientific community at large. 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. The Children’s Hospital of Los Angeles study site will enroll participants from across the Greater Los Angeles region, where the prevalence of legal and illegal non-opioid drug use is high, enabling researchers to recruit from diverse, high-risk populations.

NOFO Title: Strategic Alliances for Medications Development to Treat Substance Use Disorders (R01Clinical Trial Optional)
NOFO Number: PAR-19-318
Summary:

Given recent increases in co-use of opioids and methamphetamine, there is a dire need for novel treatment strategies that prevent relapse to drug use in both opioid use disorder (OUD) and methamphetamine use disorder (MUD). The localization of certain receptors for the neurotransmitter glutamate—metabotropic glutamate receptor subtypes 2 and 3 (mGlu2/3)—and the mechanism through which they transmit signals, strongly suggest that activation of both of these receptors will effectively treat multiple symptoms that contribute to relapse, such as responsiveness to drug cues, physical withdrawal symptoms, neuroinflammation, and sleep disturbances. This project seeks to evaluate molecules that can activate mGlu2/3 receptors without binding to the same site as glutamate (i.e., positive allosteric modulators) as a novel pharmacological treatment for preventing relapse to OUD. The research also will examine the potential of such modulators for treating MUD.

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

The U.S. is in the midst of a devastating opioid epidemic. Since 1999, the number of overdose (OD) deaths involving opioids has quadrupled. These trends are magnified among American Indians/Alaska Natives (AI/ANs) compared to other racial/ethnic groups. AI/ANs are second only to Whites in the rate of OD mortality (8/100,000 versus 12/100,000 deaths, respectively). Medications for opioid use disorder (OUD; i.e., methadone, buprenorphine and naltrexone) are considered the most effective treatment, reducing mortality and increasing abstinence and retention. However, numerous barriers limit the uptake of medications for OUD in tribal communities and within urban treatment settings serving AI/AN individuals. This is a two-phase formative research study to develop and test an implementation intervention for programs to provide medications to treat OUD specifically with AI/AN consumers. The objective of Phase I (12 months) is to develop a culturally centered implementation intervention to integrate medications for opioid use disorder (MOUD) into health care/addiction specialty settings. The objective of Phase II (24 months) is to conduct a preliminary test of the implementation intervention at four sites serving AI/AN communities. Community-based participatory research (CBPR) methods will be used throughout both phases. This study will help with decreasing stigma and increase the utilization of MOUD in health care settings that serve AI/AN populations.

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:

Although effective, current pharmacotherapies for opioid use disorder (OUD) present serious limitations. For example, methadone, a mu opioid receptor (MOP) full agonist, has significant abuse liability and causes withdrawal after chronic use, while buprenorphine (Bup), an MOP partial agonist and kappa opioid receptor (KOP) antagonist, produces limited respiratory depression and is less effective than methadone in reducing drug use, craving, and relapse. To address the limitation of currently available MATs, this project uses a phased plan that will fast-track the IND development of a next-generation medication for OUD based on small-molecule compounds targeting the nociception opioid receptor (NOP)—with no misuse or dependence liability—that have shown promising efficacy in reducing oxycodone intake in rhesus monkeys trained to self-administer, with efficacies similar to that of buprenorphine. The project’s ultimate goal is to file an IND application for an NOP agonist as a promising new approach to treat illicit and prescription OUD that may offer an alternative to buprenorphine.

NOFO Title: Notice of Special Interest to Encourage Eligible NIH HEAL Initiative Awardees to Apply for PA-20-222: Research Supplements to Promote Diversity in Health-Related Research (Admin Supp - Clinical Trial Not Allowed)
NOFO Number: NOT-NS-20-107
Summary:

RADOR-KY is a near real-time, state-wide surveillance system to monitor prevention and treatment services for opioid use disorder (OUD). This project will fill gaps in this system by capturing data from agencies receiving state funding to provide treatment and support services for people with OUD. Access to the additional data will help expand and improve surveillance dashboards being used to coordinate and target resources for preventing overdose deaths.

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 United States has seen dramatic increases in fatal overdoses due to heroin, counterfeit prescription drugs, and cocaine adulterated with fentanyl or fentanyl-like analogs. Current medications may not be sufficient to address the opioid overdose epidemic. As a complementary strategy, the researchers plan to develop vaccines against fentanyl and fentanyl-like compounds to reduce their abuse liability and the growing incidence of fatal overdoses. This research team has already developed vaccines against heroin and oxycodone that stimulate the production of antibodies effective in reducing opioid distribution to the brain, opioid-induced behaviors, and opioid-induced respiratory depression and have identified a promising fentanyl vaccine candidate cued up for optimization. Successful completion of an anti-fentanyl vaccine development project could offer a long-lasting, safe, and cost-effective intervention complementary to medication-assisted treatment (MAT) and may reduce overdoses in opioid users as well as protect people in professions (e.g., law enforcement, airport security, postal workers) at risk of accidental exposure to fentanyl and fentanyl analogs.

NOFO Title: HEAL Initiative: HEALthy Brain and Child Development Data Coordinating Center (U24)
NOFO Number: RFA-DA-21-023
Summary:

The HEALthy Brain and Child Development National Consortium (HBCD-NC) Data Coordinating Center (HDCC) will provide data management and oversight to all HBCD-NC sites to ensure the consortium’s primary objective of establishing a normative template of developmental trajectories over the first 10 years of life is met. The HBCD-NC will collect neural, behavioral, physiological, and psychological measures, as well as biospecimens, to characterize neurodevelopmental trajectories. The HDCC will coordinate data collection, data quality, data harmonization, data sharing, and data analysis efforts that are central to the consortium’s ability to implement a common research protocol. The HDCC will assemble all data across the consortium sites and distribute a comprehensive and well curated research dataset to the scientific community at large. The HDCC is tightly integrated with the HEALthy Brain and Child Development Administrative Core (HCAC) and includes a multi-institution investigative team at the University of Minnesota, University of California, San Diego, and Washington University at St Louis.

NOFO Title: HEAL Initiative: Pilot & Feasibility Trials to Improve Prevention and Treatment Service Delivery for Polysubstance Use (R34 Clinical Trial Optional)
NOFO Number: DA22-048
Summary:

Young adults (18 to 26) with a substance use problem have the highest rates of polysubstance use among all age groups. At the same time, individuals in this age group (especially in rural areas) are generally lacking in recovery capital: resources to help them recover from substance use, such as vocational or educational skills. This project will assess the feasibility and acceptability of “Launch,” which uses parental and peer recovery support to increase recovery capital for young adults with polysubstance use. The intervention will use coaching as well as contingency management, a treatment approach in which individuals receive tangible rewards as incentives for desired behaviors such as abstinence. If successful, the findings will inform a future large-scale trial assessing the effectiveness of this approach.

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

Expanding access to naloxone in the community through the pharmacy can be a critical mechanism for extending this lifesaving medication’s reach. This study will partner with two large retail pharmacy chains and integrate two interventions that provide knowledge and training for pharmacists to identify and effectively engage with patients who may be at high risk for an opioid overdose. The interventions will be combined into a cohesive educational program, implemented in 160 community pharmacies and tested for effectiveness. Study findings will create a generalizable, evidence-based training and toolkit for pharmacists caring for patients who use prescribed or illicit opioids, in more than 40 states adopting or expanding pharmacy naloxone.

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

According to SAMHSA’s 2017 National Survey on Drug Use and Health (NSDUH), 11.4 million persons in the U.S. report past-year opioid misuse; out of them, only 2.1 million individuals met criteria for an OUD. Very little is known about efficacious interventions for those who do not meet criteria for moderate/severe OUD (i.e., subthreshold OUD). The prevalence of subthreshold OUD in primary care settings is 5 percent to 10 percent, with higher rates (21 percent to 29 percent) among those receiving prescribed opioids. Although they are at high risk of developing moderate/severe OUD and/or dying from an overdose, little or no empirical evidence exists for pragmatic prevention interventions that can be adopted at integrated general medical settings. To study the efficacy of prevention interventions to arrest the progression from risky opioid use, researchers will test the efficacy of a STOP intervention in primary care settings. STOP adopts an early intervention approach, based on a collaborative care model to prevent progression to moderate/severe OUD, and consists of a practice-embedded nurse care manager who provides patient education and supports the primary care provider (PCP) in engaging, monitoring and guiding patients who have risky opioid use; brief advice delivered to patients by their PCP; and phone counseling of patients by behavioral health providers to motivate and support behavior change. Researchers will determine whether STOP reduces risky opioid use and examine the impact of STOP on progression to moderate/severe OUD, overdose risk behavior and overdose events in adults with risky use of illicit or prescription opioids.