Funded Projects

NOFO Number: PA-18-591
Summary:

Neonatal opioid withdrawal syndrome (NOWS) has emerged as a tragic by-product of the opioid epidemic. Newborns whose mothers used opioids while pregnant can experience symptoms of opioid withdrawal in the days following birth, such as tremors, irritability, seizures, sleep, digestive, and feeding problems. However, little is known about the effect of antenatal opioid exposure on longer-term infant development over time. To address this gap in understanding, the ACT NOW Longitudinal study is examining a crucial developmental period from birth to two years of life through a comprehensive battery of assessments, including MRI imaging, neurodevelopmental behavioral assessments, and family report measures. This longitudinal cohort study is projected to include a total of 375 infants, 250 who were exposed to opioids and 125 matched controls.

NOFO Title: Data Coordinating Center for the NICHD Cooperative Multicenter Maternal Fetal Medicine Units Research Network (U10)
NOFO Number: RFA-HD-13-014
Summary:

Cesarean deliveries are the most commonly performed surgical procedure in the United States. Opioids are almost universally used for post-cesarean analgesia management. Studies suggest that most women are prescribed more tablets at discharge than needed. These often go unused, providing an important reservoir contributing to the opioid crisis. Physicians struggle to prescribe and dose postoperative opioids appropriately while tackling the real needs of acute pain from surgery. Without literature to guide obstetric providers on appropriate amounts of opioids to prescribe upon discharge, actual prescription amounts nationally vary widely by up to 65 tablets. To improve post-cesarean opioid prescribing practices without compromising pain management, the study will test an individualized, patient-empowered approach for pain management and opioid prescription quantity. This is a noninferiority randomized trial of 5,500 women with a cesarean delivery who will be randomized prior to discharge.

NOFO Title: Opioid Use Disorder in Pregnancy (R01)
NOFO Number: RFA-HD-18-036
Summary:

Opioid use disorders (OUDs) in pregnancy are a U.S. public health crisis; the current standard of care is treatment with an opioid agonist such as buprenorphine (BPH), which has an associated risk for neonatal abstinence syndrome (NAS) and possible long-term neurodevelopmental consequences. As a novel treatment option for OUD in pregnancy, naltrexone would not expose the developing fetus to opioids, greatly reducing the risk for NAS and potentially improving maternal and infant outcomes. This study will evaluate the safety, efficacy, pharmacokinetics, and pharmacogenomics of naltrexone for pregnant women with OUDs, evaluating comprehensive mother-infant outcomes throughout the pregnancy and first year after birth. It will enroll 50 pregnant women stabilized pre-pregnancy on extended-release naltrexone (XR-NTX) and 50 comparison women on BPH from Boston Medical Center and the University of North Carolina in this multi-center prospective comparative cohort study.

NOFO Title: Opioid Use Disorder in Pregnancy (R01)
NOFO Number: RFA-HD-18-036
Summary:

This study will challenge current clinical approaches to managing the pregnant woman with opioid use disorder. Dosing of buprenorphine (BUP) in pregnant women is based on studies in non-pregnant subjects, which suggests that symptoms of withdrawal occur when plasma BUP concentrations are < 1ng/ml. No such data exist for pregnant women, but this is a prerequisite for defining an appropriate dosing regimen of BUP in pregnant women. We will define this threshold by monitoring women undergoing mild, medically directed withdrawal. The Clinical Opioid Withdrawal Scale score and the Finnegan score for NAS are key to defining when withdrawal occurs and thus dictate treatment in mother and baby. Neither scoring system is based on plasma BUP concentrations and thus, may not reflect true opioid withdrawal. This proposal aims to develop physiologic-based scoring systems that refine the accuracy of diagnosis and optimize treatment.

NOFO Title: NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)
NOFO Number: PA-18-489
Summary:

This project aims to develop a novel abuse deterrent formulation (ADF) that will be uniquely designed to prevent abuse of the prescription pill. The study will focus on the development of the ADF with design aspects specifically focused on abuse through insufflation, smoking, injection, and taking multiple pills. The study will also validate the design by putting the pill through a rigorous test following the procedures outlined by the FDA Abuse-Deterrent-Opioids-Evaluation and Labeling guidelines. The study could result in the development of a novel ADF that will be resistant to a wide range of tampering, resulting in a safer formulation and pill design.

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

The objective of the HEALthy Brain and Child Development (HBCD) Prenatal Experiences and Longitudinal Development (PRELUDE) multi-site consortium is to characterize typical brain development from birth through childhood. All sites in this consortium will measure the influence of key biological and environmental factors on child social, cognitive, and emotional development. Researchers will assess how prenatal exposure to opioids and other substances, as well as other adverse environmental factors, affect brain development and other child health outcomes. The Cincinnati Children’s Hospital study site is in a region hit hard by the opioid crisis and has a large catchment area that includes many rural counties in Ohio, Kentucky, Indiana, and West Virginia.

NOFO Title: HEAL Initiative: HEAL Data2Action Data Infrastructure Support Center
NOFO Number: RFA-DA-22-046
Summary:

This project will evaluate a previously developed harm reduction intervention that addresses the needs of women who use drugs in an urban environment. The approach uses a mobile van to offer naloxone, fentanyl test strips, and other harm reduction supplies – along with necessities such as food and clothing, brief trauma-informed counseling, and referrals to drug treatment, medical care, and social services. This research aims to test the impact of an intervention that may increase access to harm reduction services for women, as well as assess how to put it into place.

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: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: RFA-DA-19-002
Summary:

Opioid use disorder (OUD) is a serious public health problem that is associated with high rates of morbidity and mortality. The proposed Phase 1a/1b studies are designed to evaluate a novel treatment strategy for OUD. Specifically, the safety, immunogenicity and preliminary efficacy of a vaccine (OXY-KLH) targeted against oxycodone (Study 1) and a vaccine (M-KLH) targeted against heroin/morphine (Study 2) will be evaluated in participants diagnosed with OUD.

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:

Though prenatal exposure to opioids and other substances have adverse effects on neurodevelopment, advances in neuroimaging and developmentally sensitive phenotypic measurement now enable characterization of typical and atypical brain-behavior pathways on an unprecedented scale. The Brains Begin Before Birth (B4) Midwest Consortium, a partnership of neuroscience, substance use, perinatal mental health, and child welfare scientists at Washington University School of Medicine (WUSM) and neuroscience, bioethics, pediatric population health, maternal-fetal, and addiction scientists at Northwestern University (NU). This regional consortium will leverage the contrasting approaches of Illinois (punitive) and Missouri (non-punitive) to prenatal opioid use, providing a platform for examining the impact of jurisdictional variations on science and practice. The consortium provide a framework for addressing three major areas of challenge: (1) legal/ethical, (2) recruitment/retention, and (3) imaging/assessment methods.

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:

Levo-alpha-acetylmethadol (LAAM) offers numerous behavioral and clinical advantages for select opioid use disorder (OUD) patients who do not respond to standard treatment. While LAAM was withdrawn from the market despite being approved for OUD treatment, this project seeks to develop novel, patentable, convenient dosage forms of LAAM, including novel LAAM oral dosage formulations and novel buccal film formulations of LAAM. Morphology, mechanical property, drug release kinetics, and stability of the oral dosage and buccal film formulations will be characterized to determine the instant release or steady release of LAAM, respectively. The two lead LAAM formulations with adequate release and stability profiles will be chosen through optimization studies both in vitro and in vivo. A human pharmacokinetic/pharmacodynamic study will then be carried out on the two selected formulations.

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:

The goal of this project is to discover potential targets for emergency department-based interventions that could enhance access to addiction treatment among Black and Latino individuals, who face significant disparities in access to ongoing addiction treatment. Through qualitative interviews with Black, Latino, and non-Latino White patients receiving emergency department-initiated buprenorphine, the research will identify patterns of barriers and facilitators for continuation of opioid use disorder treatment outside of the emergency department through a referral. The study will also evaluate differences in factors previously identified as predictors of worse treatment outcomes in these patient groups, including opioid overdose, polysubstance use, major depressive disorder, and stigma.