Funded Projects

NOFO Title: Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
NOFO Number: PAR-20-092
Summary:

The nation’s opioid epidemic remains a public health emergency, marked by high rates of opioid use and misuse among adults and a correlated rising incidence of neonatal opioid withdrawal syndrome (NOWS) in infants exposed to opioids before they are born. There are currently no pharmacotherapies approved by the Food and Drug Administration (FDA) for the treatment of NOWS. This research will complete manufacturing and clinical trial activities to evaluate and support FDA approval of a pediatric-appropriate formulation of lofexidine, a non-opioid medication approved for mitigation of opioid withdrawal symptoms in adults, as a first line-therapy in NOWS patients through two clinical trials to (1) identify an optimal dosing regimen of lofexidine for treatment of NOWS, and (2) evaluate the risks and benefits of its use in improving withdrawal symptoms, limiting infant exposure to other off-label narcotic medications and shortening the infant’s overall stay in the hospital.

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 research dataset to the scientific community. 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. This study will take place at Oklahoma State University Center for Health Sciences and recruit diverse people from an urban area, including American Indian populations.

NOFO Title: Research Supplements to Promote Diversity in Health-Related Research (Admin Supp - Clinical Trial Not Allowed)
NOFO Number: PA-21-071
Summary:

Although there are effective prevention and treatment programs and services to address opioid misuse, opioid use disorder, and overdose, gaps remain between those needing and those receiving prevention and treatment. There is a need to better understand how to make these programs and services most effective at a local level, a problem being addressed by the HEALing Communities Study. This project supports a scientist from a group underrepresented in biomedicine to continue ongoing work to test the impact of an integrated set of evidence-based practices across health care, behavioral health, justice, and other community-based settings.

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-19-019
Summary:

One novel approach to address the opioid crisis is predicting the likelihood of retention in treatment for opioid use disorder (OUD) by assessing someone?s risk of early departure from treatment. Current methods rely on providers intuition to identify when an individual is at risk of leaving treatment early in order to intervene. This intervention, when it happens, often comes too late. Mobile health (mHealth) and Machine Learning (ML) predictive analytics offer a new opportunity to personalize OUD treatment, improve retention in OUD care, and mitigate the risk of relapse and overdose episodes. Project Motivate will combine physiological and behavioral data from disparate sources in order to predict when an individual is at risk of early departure from OUD treatment. If successful, results of the study will save lives, and lower medical costs, municipal emergency response costs, recidivism, workplace accidents, lost workplace productivity and costs to families.

NOFO Title: Notice of Special Interest: HEAL Supplements to Improve the Treatment and Management of Common Co-occurring Conditions and Suicide Risk in People Affected by the Opioid Crisis
NOFO Number: NOT-MH-20-025
Summary:

The United States is in the middle of two intertwined epidemics. Suicide and overdose deaths are at record levels. Opioid use disorder and mental illness are major contributors to both, with the highest death rates seen in people with co-occurring disorders (COD). This competitive revision tests whether enhancements to the collaborative care (CC) model adapted for co-occurring disorders improves retention in medication treatment and decreases suicide and overdose risk. The three additional components include: (1) education of family members about addiction and medication treatment; (2) training for family members to administer naloxone and on how to reduce opioid risk behaviors, and (3) implementation of Caring Contacts, a suicide prevention intervention. This study will examine patient and family member attitudes toward overdose education and naloxone in the population with COD; examine and then intervene with family members around patients? use of medication; and test in the COD population the effectiveness of universal suicide and overdose prevention programs.

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:

Buprenorphine has been shown to be is an effective method for treating Opioid Use Disorder (OUD). However, despite its success, treatment retention rates are notoriously low ? about half of those seeking treatment will have dropped out within the first 6 months. One factor known to negatively impact treatment adherence is stigma. This stigma derives from not only being viewed as individuals with OUD, but even as individuals seeking medications for OUD as these medications often include other forms of opioids. Additionally, individuals with OUD often suffer from other conditions, including psychiatric illness, leading them to live with multiple stigmatized identities. This study will develop tools to assess stigma associated with OUD, seeking medical treatment for OUD, and mental health. This knowledge will then be used to adapt the parent award?s mobile Health intervention intended to overcome stigma barriers and increase adherence to buprenorphine treatment for OUD.

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: Research Networks for the Study of Recovery Support Services for Persons Treated with Medications for Opioid Use Disorder (R24 Clinical Trial Optional)
NOFO Number: RFA-DA-20-014
Summary:

The opioid epidemic in the United States is associated with alarming rates of overdose and overdose deaths. Medication Assisted Treatment (MAT), in combination with psychosocial intervention, is the most effective treatment for OUD; however, many individuals are unable to access treatment, are not sufficiently retained in treatment, or experience barriers that prohibit their participation in treatment. A multipronged approach is needed that includes 1) development of integrated networks of care, both formal and informal, to better address the needs of individuals with OUDs and 2) measures of the efficacy of these integrated networks for addressing the needs of individuals with OUD. This project will build a learning collaborative to address gaps in knowledge about the delivery, sustainability, and assessment of recovery service for individuals on MAT. The collaborative will foster collaboration and communication between stakeholders and with the larger community of research and providers interested in improving the delivery of OUD recovery support services. This community-academic partnership will address the lack of evidence regarding effective recovery support services.

NOFO Title: Notice of Special Interest: HEAL Supplements to Improve the Treatment and Management of Common Co-occurring Conditions and Suicide Risk in People Affected by the Opioid Crisis
NOFO Number: NOT-MH-20-025
Summary:

Mortality and morbidity related to suicidal behavior and opioid use disorder (OUD) have increased significantly over the past decade. These two public health crises are intertwined at multiple levels. Medications for OUD, especially buprenorphine, have been shown to decrease opioid use and reduce the multiple negative consequences of OUD, including fatal and nonfatal overdose, criminal justice involvement, infectious complications, and misuse of other substances. In addition, small randomized trials of buprenorphine treatment in treatment-resistant depression (with or without co-occurring OUD) suggest that buprenorphine reduces depressive symptoms and suicidal ideation. This large study will evaluate the effects of starting buprenorphine treatment on self-harm and suicide attempt among people with opioid use disorder, including those with and without co-occurring mental health conditions or other known risk factors for suicidal behavior. Comprehensive health records data from four large health systems serving a combined member/patient population of approximately 11 million will be examined for the overall effect of buprenorphine treatment on subsequent self-harm or suicide attempt, including differences in effects between patient subgroups and specificity of effects to buprenorphine vs other medications.

NOFO Title: Grand Opportunity in Medications Development for Substance-Use Disorders (U01 - Clinical Trial Optional)
NOFO Number: PAR-19-327
Summary:

Opioid use disorder (OUD) is a significant public health problem in the United States. Particularly troubling is the rapid evolution of an opioid epidemic within the past decade, characterized by a surge in unintentional overdose deaths involving synthetic opioids, such as fentanyl. The current standard of care for opioid overdose is reversal with opioid antagonist naloxone. Naloxone is effective at reversing overdose from prescription opioids and heroin, but less effective when combating fentanyl, due to fentanyl?s high potency. Therapeutic monoclonal antibodies (mAbs) against fentanyl could overcome this problem by specifically preventing the drug from entering the central nervous system, averting overdose and attenuating opioid-induced respiratory depression. This study will develop and design of laboratory protocols needed to establish a Good Manufacturing Practice (GMP) process, quality assurance protocol, and stability profile for a new human mAb against fentanyl. Subsequent production of current GMP material will enable Good Laboratory Practice (GLP) toxicology studies in rats and dogs and eventually a Phase I/IIa clinical trial. This material will also be used in final opioid-induced respiratory depression studies in mice and non-human primates to confirm therapeutic efficacy of final drug product. If successful, these activities will enable filing for an investigational new drug application for this mAb candidate with the FDA.

NOFO Title: Notice of Special Interest(NOSI): HEAL Initiative: Social Network Analyses to Reduce American Indian and Alaska Native Opioid Use Disorder and Related Risks for Suicide and Mental Health Disorders
NOFO Number: NOT-DA-20-033
Summary:

American Native (AN) communities experience high rates of trauma that compromise the mental health of parents and caregivers that in turn increases their children?s risk for suicide and substance use during adolescence and young adulthood. Without intervention, this intergenerational cycle may repeat. The goal of this study is to understand opioid use, suicide, and the social network characteristics of Fort Peck Assiniboine and Sioux parents and caregivers to determine how the social network of parents/adult caregivers are related to both risk for and protection from suicide and opioid use. This supplement will examine the effectiveness of a community health worker delivered, culturally tailored prevention intervention called Wa?Kan Ye?Zah on caregiver and child behavioral and mental health outcomes and assess the benefits of culturally enhancing the intervention for caregivers? well-being.

NOFO Title: HEAL Initiative: Pharmacotherapies to Reverse Opioid Overdose Induced Respiratory Depression without Central Opioid Withdrawal (Target Validation and Candidate Therapeutic Development (R61/R33 - Clinical Trial Not Allowed)
NOFO Number: RFA-HL-20-031

NOFO Title: Notice of Special Interest (NOSI): NHLBI and NIDA Announce Availability of Administrative Supplements for HEAL Awardees to Address Sleep Impairments in OUD Treatment Response and Recovery Outcomes
NOFO Number: NOT-HL-20-746
Summary:

Opioid use disorder, a chronic and relapsing disease, is a significant and escalating public health concern. But, despite the availability of approved pharmacotherapies and promising therapeutic interventions, the high rates of relapse indicate a critical need for a better understanding of the factors that contribute to relapse to opioids, and for the development of new treatment approaches. Sleep problems are a common symptom in most substance use disorder syndromes, including opioid use disorder (OUD), but they are severely undertreated, partly because the standard hypnotic medications used to treat sleep disorders are themselves addictive. This study will investigate whether activating the glucagon-like peptide-1 receptor pathway can help reduce craving while improving sleep in OUD patients. The FDA-approved medication liraglutide, a GLP-1R agonist, is currently approved to treat Type II diabetes mellitus and obesity in humans. This proposal for a supplemental study will add polysomnography, the gold-standard for evaluating sleep architecture, to an ongoing study. If successful, this study will provide a strong rationale for conducting a full multi-site, Phase III clinical trial.