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-19-020
Summary:

The primary cause of death associated with opioids is opioid-induced respiratory depression, and there is currently no way to prevent this condition. The goal of this research is to develop a therapy to prevent opioid-induced respiratory depression without disrupting opioids’ analgesic effects. Previous research has shown that the hormone leptin, which suppresses appetite and increases metabolic rate, also stimulates breathing. This research project in a mouse model will test if the novel, brain-penetrant leptin receptor-binding protein E1/Aca can prevent fentanyl-induced breathing failure without diminishing fentanyl’s analgesic effects.

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

Four out of five youth in the juvenile justice (JJ) system show evidence of being under the influence during their offenses, and more than half test positive for substances at the time of their arrest. Preventive intervention approaches that can be easily implemented within JJ settings may offer greater access to substance use care as well as increase families’ motivation to comply with court referrals to seek further services. It is especially important to evaluate interventions for court-involved, non-incarcerated (CINI) juveniles, as these youth account for two-thirds of those arrested; however, the bulk of extant research has been conducted with detained or incarcerated youth. In this application for supplemental funding, we capitalize on our parent grant (Brief Individual and Parent Interventions for Marijuana Misuse in Truant Adolescents) by proposing to develop an adjunctive, targeted preventive intervention for marijuana-using, JJ youth who are at elevated risk for illicit opioid use. The goal will be to develop a protocol for a single-session, parent-adolescent preventive intervention to decrease the likelihood of illicit opioid use in CINI adolescents. This formative work will culminate in a draft intervention manual.

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

We propose to estimate the impact of expanded access to medication-assisted treatment (MAT) in prisons and jails on post-release rates of overdose. Our approach will use agent-based modeling, data collected through the parent study, existing surveillance data, and recently published data from similar settings to understand how different MAT interventions in the prison and jail setting impact overdose death post-release. We will examine the impact of standard of care/no intervention, providing access to depot-naltrexone alone, providing access to all three MATs to only those who were prescribed it prior to incarceration, and comprehensive provision of all three MATs on post-release rates of overdose. These models will incorporate advanced methodological techniques that will allow for the investigation of engaged treatment, program attrition, and other complex events on a population level. This study’s findings may be used by health agencies, policymakers, and correctional systems to inform their efforts to expand MAT access.

NOFO Title: HEAL Initiative: HEALthy Brain and Child Development Study (Collaborative U01- Clinical Trial Not Allowed)
NOFO Number: RFA-DA-21-020
Summary:

This study aims to determine how exposure to opioids and other substances affects the developing fetal brain and shapes later child cognitive outcomes. Researchers will collect neuroimaging and behavioral data, as well as measures of environmental exposures related to social equity, COVID-19, and socioeconomic factors. The project will reduce traditional barriers to participation by using innovative data collection methods and mobile labs to bring the research to underrepresented and marginalized communities. This approach aims to clarify the impact of substance exposure on child development through an equitable approach to research, with generalizable findings. The study will take place at Rhode Island Hospital, where participants will be drawn from a largely rural population.

NOFO Title: HEAL Initiative: Development of Therapies and Technologies Directed at Enhanced Pain Management (R43/R44 – Clinical Trial Not Allowed)
NOFO Number: RFA-NS-20-011
Summary:

Chemokines (hormones of the immune system that mediate innate immune inflammation) enhance pain, reduce opioid analgesia, and promote drug-seeking behavior and addiction, giving them a central role at the crossroads of chronic pain and the opioid crisis. Blocking chemokines (rather than opioid receptors) provides an exciting treatment opportunity for both pain and opioid use disorder. This research continues previous work studying the efficacy of RAP-103, a small, orally stable chemokine receptor blocker. The previous research has shown that RAP-103 is safety and effective in preclinical models that mimic human drug-taking. This research will now optimize the dose required to achieve decreased motivation to maintain opioid use, establish manufacturing scale-up feasibility, provide RAP-103 for safety testing in animals, and conduct stability testing of RAP-103 toward the goal of submitting an Investigational New Drug application to the FDA.

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

Current rates of prescription opioid misuse are rising to epidemic levels among adults. These rates may be even higher among adolescents and young adults (AYAs), who have elevated levels of substance exploration and misuse during this precise developmental period. AYAs who are exposed to opioids via legitimate prescriptions by age 18 are at increased risk for misuse after high school. However, there is a substantial gap in our knowledge of what factors might contribute to the development of misuse and related poor outcomes in these high-risk youth. Identifying factors that convey risk for increasing opioid use and problematic use would inform AYA models of opioid abuse and inform the development of preventive interventions to modify risk in medical settings, which are a unique point of entry into opioid use, and a key setting in which to examine AYA outcomes. We will use a developmental model of the impact of opioid exposure by legitimate prescription during late adolescence, with consideration for pain and psychological characteristics of the individual within the psychosocial (family, peer, educational and work context). Determining mechanisms and moderators of risk during this developmental transition will provide critical information for the design of interventions aimed at reducing opioid use disorders in at-risk AYA.

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

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:

Rates of neonatal abstinence syndrome have reached a staggering 6.5 per 1,000 births nationwide, creating an urgent need to identify how in-utero exposure to opioids and associated risk factors influence the developing brain. A multidisciplinary team will address these challenges in Oregon, a state particularly hard hit by the opioid epidemic. Through linking sites, the impact of the Phase I project is enhanced and will provide critical information to support a national-level effort for Phase II of the HEALthy Brain and Child Development Study. Aim 1 will develop, implement, and evaluate innovative recruitment and retention strategies for high-risk populations. Aim 2 will address anticipated challenges of the planned Phase II study by implementing and evaluating a multi-site, standardized research protocol including multimodal MRI of placenta, fetus, neonate, and 24-month-old brain; biospecimen collection; and assessment of substance use and other key domains. Aim 3 will evaluate data acquisition, processing, and statistical considerations to maximize data quality, usability, and integration across sites.

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:

Rates of neonatal abstinence syndrome have reached a staggering 6.5 per 1,000 births nationwide, creating an urgent need to identify how in-utero exposure to opioids and associated risk factors influence the developing brain. A multidisciplinary team will address these challenges in Oregon, a state particularly hard hit by the opioid epidemic. Through linking sites, the impact of the Phase I project is enhanced and will provide critical information to support a national-level effort for Phase II of the HEALthy Brain and Child Development Study. Aim 1 will develop, implement, and evaluate innovative recruitment and retention strategies for high-risk populations. Aim 2 will address anticipated challenges of the planned Phase II study by implementing and evaluating a multi-site, standardized research protocol including multimodal MRI of placenta, fetus, neonate, and 24-month-old brain; biospecimen collection; and assessment of substance use and other key domains. Aim 3 will evaluate data acquisition, processing, and statistical considerations to maximize data quality, usability, and integration across sites.

NOFO Title: HEAL Initiative: Harm Reduction Policies, Practices, and Modes of Delivery for Persons with Substance Use Disorders (R01 Clinical Trial Optional)
NOFO Number: RFA-DA-22-046
Summary:

People who use drugs often have other medical problems that cause them to visit an emergency department frequently. This project will develop and test an intervention aimed at reducing health risk among Black people who use drugs that visit an urban emergency department for care. The intervention will be delivered by people with lived experience of drug use and tailored to meet the unique needs of Black people who use drugs.

NOFO Title: HEAL Initiative: Research to Foster an Opioid Use Disorder Treatment System Patients Can Count On (RM1 - Clinical Trial Optional)
NOFO Number: RFA-DA-23-046
Summary:

Medicaid covers the cost of treatment for opioid use disorder (OUD) for most individuals who need it, including minoritized populations and those with risk factors related to low income, education, and employment. The Medicaid Outcomes Distributed Research Network has supported efforts to improve OUD treatment by developing novel measures of treatment quality and examining effects of treatment quality on overdoses. Using this network, this project will leverage university-state partnerships in 12 states to inform quality improvement initiatives and Medicaid policy. The research will develop provider-level quality measures for OUD using Medicaid administrative data and measure patient-reported outcomes. The research will also look for approaches to use claims-based quality measures and practice-level quality improvement strategies to improve treatment outcomes for people with OUD.

NOFO Title: HEAL Initiative: Notice of Special Interest (NOSI) regarding the Availability of Administrative Supplements to Support Strategies to Reduce Stigma in Pain Management and Opioid Use Disorder (OUD) and Treatment
NOFO Number: NOT-OD-20-101
Summary:

While advances in cancer treatment have increased survival rates, these patients often suffer from chronic cancer pain. Prescription opioids are often prescribed during active cancer treatment, but their long-term use for chronic cancer pain is associated with risk for opioid use disorder and risk for stigmatization associated with emotional distress, suboptimal health behaviors and coping strategies, and difficult patient-provider communication. This study aims to conduct qualitative interviews exploring prescription opioid and chronic pain stigma in cancer survivors with moderate-to-severe pain, caregivers, and clinicians who treat patients with chronic cancer pain, including oncologists, primary care providers, pain management specialists, and palliative care physicians. An analysis of potential contributors to stigma in cancer survivors will be completed to support development of multi-level behavioral interventions to reduce stigma and explore long-term health outcomes from such interventions.