Funded Projects

NOFO Title: HEAL Initiative: Early Phase Pain Investigation Clinical Network - Specialized Clinical Centers (U24 Clinical Trials Not Allowed)
NOFO Number: RFA-NS-19-025
Summary:

The Medical University of South Carolina (MUSC) Specialized Clinical Center (Hub) of the Early Phase Pain Investigation Clinical Network (EPPIC-Net) will provide a robust and readily accessible infrastructure for rapid implementation and performance of high-quality comprehensive studies of novel treatments for patients with a wide variety of pain conditions. The MUSC-Hub will harness multidisciplinary clinical, research, statistical, and data management expertise to provide the scientific leadership and infrastructure required to design and conduct multisite Phase II clinical trials, biomarker validation studies, and deep phenotyping of patient populations as part of the EPPIC-Net with the overall goal of accelerating the development of new therapies for patients with acute and/or chronic pain.

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

Very little research has been conducted on better understanding of phenotypic characterization of individuals with OUD (beyond DSM-5 diagnoses) and how these features predict illness severity, treatment retention or outcomes. The primary objective of the deep phenotyping study is to provide a comprehensive phenotypic characterization (e.g., domains of negative affect, reward salience, cognitive control, mental health) of a heterogeneous sample of individuals (n = 1,000) who currently meet one or more DSM-5 diagnostic criteria for OUD and are in treatment for OUD. In a subset of this sample (n = 100), the investigators conduct digital phenotyping to examine the utility of ecological momentary assessment (EMA), digital sensing and social media to predict retention, medication adherence and opioid use outcomes in patients receiving buprenorphine for OUD. It is anticipated that this foundational study will inform the feasibility and utility of such assessments that can be successfully embedded into imminent and future CTN and other OUD clinical trials.

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:

The Planning for the HEALthy Early Development Study will contribute to the design and recommended protocol for a future large-scale, multi-site research study to prospectively examine human brain, cognitive, behavioral, social, and emotional development of children beginning prenatally through ages 9–10 and to determine the impact of maternal pre- and postnatal substance use on short- and long-term development of children. The planning study will link investigators across 6 research sites who have complementary experience and expertise in the areas that are essential to designing the study. Planning activities will be accomplished using a coordinated set of 10 working groups. By the end of the planning phase, the 6 consortium sites will have produced and tested a recommended protocol for the future multi-site study and will have established feasibility of carrying out the study protocol at each of the 6 linked sites.

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 current studies are designed to examine a novel approach to treating OUD, namely use of a vaccine (OXY-KLH) targeted against oxycodone, one of the most commonly misused prescription opioids, and a vaccine (M-KLH) targeted against heroin/morphine. The researchers will evaluate the safety, immunogenicity, and preliminary efficacy of OXY-KLH and M-KLH. Overall, the proposed studies will provide a great deal of information about the safety and potential efficacy of the vaccines in reducing the addiction liability of opioids, which will be administered in a controlled laboratory setting. If the outcomes of the proposed studies with OXY-KLH and M-KLH are favorable, development of the bivalent vaccine (OXY-KLH plus M-KLH) that will target oxycodone and heroin will proceed. The long-term goal of this research is to develop a multivalent vaccine directed against oxycodone, heroin, and other relevant opioids.

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: 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: 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: HEAL Initiative: Behavioral Research to Improve MAT: Behavioral and Social Interventions to Improve Adherence to Medication Assisted Treatment for Opioid Use Disorders (R61/R33 Clinical Trial Optional)
NOFO Number: RFA-AT-19-006
Summary:

Medications for the treatment of opioid use disorders (MOUD) are effective at reducing opioid use, opioid overdose risk, and opioid-related deaths; however, retention and adherence to MOUD treatment, particularly buprenorphine (BUP), are discouragingly low. The objective of the current research is to adapt and extend a cognitive behavioral therapy-based short message system (SMS) intervention (TXT-CBT) to address MOUD treatment retention and adherence using the imFREE (Interactive Messaging for Freedom from Opioid Addiction) platform. imFREE builds upon the efficacious SMS-based TXT-CBT intervention, with content addressing retention and adherence to BUP, including mitigating risk factors for dropout, and features to notify social and provider support contacts in the face of treatment discontinuation and/or other indicators of relapse and overdose risk. By providing support to maximize BUP treatment adherence, coupled with skills to prevent relapse, imFREE may provide a cost-effective, easily deployable strategy for OUD treatment and prevention of overdose deaths.

NOFO Title: NIDA Small Research Grant Program (R03 Clinical Trial Required)
NOFO Number: PA-18-634
Summary:

Exposure to opioid analgesics during medical care is a key driver of the opioid epidemic. Such exposures are widespread. Yet opioids remain essential first-line agents in treating pain, and it remains vital that pain be appropriately managed. Non-opioid pain treatments help to resolve the opioid/pain conflict. This project will examine the opioid-sparing and pain-relieving potential of a novel, non-pharmacological treatment for pain, using the effects of green light exposure to reduce pain and thereby reduce the quantity of opioids needed for pain relief.

NOFO Title: HEAL Initiative: Tissue Chips to Model Nociception, Addiction, and Overdose (UG3/UH3 Clinical Trial Not Allowed)
NOFO Number: RFA-TR-19-003
Summary:

This project will build overdose models for fentanyl, methadone, codeine, and morphine in a multi-organ system and evaluate the acute and repeat dose, or chronic effects, of overdose treatments as well as off-target toxicity. Researchers developed a system using human cells in a pumpless multi-organ platform that allows continuous recirculation of a blood surrogate for up to 28 days. They will develop two overdose models for male and female phenotypes based on pre-B?tzinger Complex neurons and will integrate functional immune components that enable organ-specific or systemic monocyte actuation. Models for cardiomyopathy and infection will be utilized. Researchers will establish a pharmacokinetic/pharmacodynamic model of overdose and treatment to enable prediction for a range of variables. We will use a serum-free medium with microelectrode arrays and cantilever systems integrated on chip that allow noninvasive electronic and mechanical readouts of organ function.

NOFO Title: PHS 2018-02 Omnibus Solicitation of the NIH, CDC, and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed)
NOFO Number: PA-18-574
Summary:

Newborn Abstinence Syndrome, which results from maternal opioid drug use prior to birth, is a serious condition that affects approximately 6% of all neonates born today in the U.S. and which is increasing rapidly in incidence because of this epidemic. Availability of a rapid screening test that can be administered at the point of care to all neonates would allow for early intervention, reducing costs of treatment and reducing pain and suffering for this vulnerable and helpless patient population. Providing a platform to accurately monitor actual levels of these drugs and their metabolites in such patients would allow better-controlled use of these pain management treatments, personalized to the needs of the individual neonate, and would reduce the probability of addiction and resulting complications, which include deleterious neurological effects. The purpose of this FastTrack SBIR project is to expand upon preliminary results that a device can sensitively and accurately detect opioids and their primary urinary metabolites in one-microliter urine samples, in less than a minute after sample introduction into the device, and adapt the device into a point-of-care instrument for use in hospitals, clinics, and other venues in which such tests are likely to be deployed.

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:

Rates of neonatal abstinence syndrome (NAS) have skyrocketed during the last decade, and estimates suggest that 5% of mothers use at least one addictive drug during their pregnancy. To address this public health crisis, multiple groups—including the American College of Obstetricians and Gynecologists and the American Academy of Pediatrics—recommend universal screening of substance use in pregnancy using standardized behavioral scoring tools. Unfortunately, such tools are often biased due to subjective scoring or self-reporting errors, and fail to identify babies who did not receive proper prenatal care. This project will develop a fast and accurate NAS screening tool that pairs a simple sample preparation protocol with a high-sensitivity panel of homogeneous enzyme immunoassays recognizing five common classes of drugs: fentanyl, morphine, amphetamine/methamphetamine, cocaine, and benzodiazepines. The potential benefits of such a system include reduced length of hospitalization for unaffected newborns, accelerated time to confirmatory results (under 2 hours), faster resolution of acute withdrawal symptoms, and improved referral to family/maternal support services.

NOFO Title: HEAL Initiative: Preventing Opioid Use Disorder in Older Adolescents and Young Adults (ages 16–30) (UG3/UH3 Clinical Trial Required
NOFO Number: RFA-DA-19-035
Summary:

The national public health opioid crisis has disproportionately burdened rural white populations and American Indian populations. To address this crisis, the Cherokee Nation and Emory University public health scientists will carry out an opioid prevention trial to be conducted in at-risk rural communities in the Cherokee Nation (in northeast Oklahoma) with populations of white and American Indian adolescents and young adults. The study will expand and integrate two established intervention approaches, consisting of community organizing and universal school-based brief intervention and referral to further enhance their effects in preventing and reducing opioid misuse. These interventions, called CMCA and CONNECT, were originally designed to target adolescent alcohol use, but showed significant beneficial effects on use of other drugs, including prescription drug misuse. The expanded, integrated interventions will be tested in a community-randomized trial with the goal of new systems for sustained implementation within existing structures of the Cherokee Nation.