Funded Projects

NOFO Title: Device-Based Treatments for Substance Use Disorders (UG3/UH3, Clinical Trial Optional)
NOFO Number: PAR-18-494
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:

There is a significant treatment gap between patients diagnosed with OUD and those who seek treatment, and only a small proportion of those seeking treatment receive MOUD. Primary care is the most common point of health care contact in the U.S. and is an important venue to address stigma, improve access to treatment and improve quality of care. Over the past decade, electronic health record (EHR)-linked Web-based point-of-care clinical decision support (CDS) systems designed to improve quality of chronic disease care have become increasingly sophisticated and successful. A Web-based and EHR-integrated OUD CDS system to offer expert guidance to primary care providers (PCPs) on the diagnosis and management of OUD was developed and piloted. This project will implement the OUD clinical decision support system in three large diverse health care systems and randomize a minimum of 30 clinics to receive the OUD-CDS intervention or usual care (UC). The project will evaluate the impact of OUD CDS on practice process measures and patient outcomes. The study will also prepare for scalability and dissemination by evaluating facilitators and barriers to implementation, determining the costs of implementation and maintenance and assessing the short-term cost impacts of the OUD-CDS.

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

New medication treatment approaches are needed to help address the severe epidemic of opioid use disorder (OUD) and opioid overdose deaths in the U.S. Currently available medications, such as methadone, buprenorphine, and extended release injection naltrexone (XR-NTX; trade name: Vivitrol), are highly efficacious, but their effectiveness in practice is limited by poor adherence, with many patients stopping treatment prematurely and relapsing. The goal of this proposal is to develop an innovative long-acting subcutaneous implanted formulation of naltrexone, the O’Neil Long-Acting Naltrexone Implant (OLANI), toward FDA approval. Expected to produce naltrexone blood levels sufficient to block the effects of opioids for 6 months after implant, OLANI circumvents the need for adherence to monthly injections with XR-NTX and could represent an important new addition to the medical armamentarium for treatment of 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:

The opioid antagonist naltrexone (NTX) is a proven treatment for opioid use disorder (OUD); however, lack of adherence is a serious limitation that has prevented NTX from reaching its maximum therapeutic potential. To address this limitation, BioCorRx is developing BICX102, a subcutaneous solid depot pellet of NTX, a single implantation of which can provide continual blockade of opioid receptors for up to 3 months. This can prevent patients from being adversely affected by almost any opioid relapse event, while improving efficacy and adherence to behavioral programs that support long-term management and recovery. This proposal comprises the steps required to achieve FDA approval. Successful development of BICX102 would result in a safe and effective 3-month subcutaneous depot pellet/implant containing NTX (1,000 mg) that would be far less reliant on patient compliance.

NOFO Title: Mechanism for Time-Sensitive Drug Abuse Research (R21 Clinical Trial Optional)
NOFO Number: PAR-19-064
Summary:

In 2018, new opiate prescribing limits (SB 273) were implemented across West Virginia to combat the opiate misuse epidemic. This study will utilize quantitative and qualitative measures to determine the effect of the recent opiate prescription laws in West Virginia, how a change in policy affects the opiate misuse epidemic, and how communities may apply this knowledge more broadly. The research team will: 1) collaborate with the West Virginia Board of Pharmacy to ascertain changes in opiate prescribing habits before and after the start of SB 273 using an interrupted time series methodology, and 2) achieve broad and deep understanding of how SB 273 has affected prescribing practices and experiences amongst primary care physicians, specialists (pan physicians, surgeons, emergency room physicians, etc.), and patients who currently or previously utilized opiate medications.

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: Development of a Device to Objectively Measure Pain (R43/R44)
NOFO Number: RFA-DA-18-012
Summary:

One of the most widely used treatments for chronic pain is opioid analgesics. Importantly, there is evidence of a pathological interaction between opioids and the immune system that can contribute to both opioid tolerance and elevated levels of pain. Chronic pain conditions for which opioids are most often prescribed have been shown to involve dysregulation of the immune system, which may contribute to pathological effects of opioid use in these patients. To address this unmet need, this study aims to develop a reliable, cost-effective, and non-invasive in vitro diagnostic assay for chronic pain with an underlying inflammatory pathology, as a blood test available in primary care settings, with the hope that doctors can use the test to identify which patients might benefit less from opioids and be more likely to become addicted.

NOFO Title: PHS 2018-02 Omnibus Solicitation of the NIH for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Required)
NOFO Number: PA-18-573
Summary:

Noninvasive brain stimulation (NIBS) may be effective in treating some forms of addiction, but the most common NIBS methods, Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS), have not been found to be effective in treating opioid use disorder (OUD). This project seeks to test the efficacy in OUD patients of Electrosonic Stimulation (ESStim™), an improved NIBS modality that combines independently controlled electromagnetic and ultrasonic fields to focus and boost stimulation currents via tuned electromechanical coupling in neural tissue.

NOFO Title: HEAL Initiative: Sleep and Circadian-Dependent Mechanisms Contributing to Opiate Use Disorder (OUD) and Response to Medication Assisted Treatment (MAT) (R01 - Clinical Trial Not Allowed)
NOFO Number: RFA-HL-19-028
Summary:

Profound sleep disturbances during abstinence have long been suspected of perpetuating vulnerability to relapse of people who misuse or are addicted to opioids. An animal model has shown that long-term sleep deficiency results in a persistent state of physiological dysregulation that is expected to modify the biology of abstinence and increase relapse potential. This study seeks to discover how persistent sleep restriction during withdrawal from opioid use increases vulnerability to relapse in the animal model by testing whether persistent sleep restriction during abstinence from opioid use is sufficient to increase opioid drug seeking. The functional outcome measure will be the degree of mitigation of opioid seeking. These studies will provide a basis for novel translational approaches to target mechanisms that are demonstrated to cause increased vulnerability to relapse.

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

This study will examine the epidemiology of injection drug use, its infectious consequences, and service accessibility among young persons who inject drugs (PWID) in 15 rural counties in Maine, New Hampshire, and Vermont, then implement an integrated telemedicine approach to treat opioid use disorder (OUD) and reduce infections and overdose. The UG3 phase will characterize the risk environment and epidemiology of OUD, its infectious complications, opioid overdose, risk behaviors, service use, and needs in young PWID in these counties. An environmental assessment of policy and infrastructure will examine available services, needs, and gaps. The UH3 phase will evaluate the effectiveness of a regionalized integrated model of expanded service delivery for rural PWID. This project will provide in-depth understanding of high-risk rural PWID, inform community response strategies, and implement a comprehensive, integrated approach to treat OUD and reduce overdose and infectious complications among PWID in the rural United States.

NOFO Title: HEAL Initiative: Sleep and Circadian-Dependent Mechanisms Contributing to Opiate Use Disorder (OUD) and Response to Medication Assisted Treatment (MAT) (U01 Clinical Trial Optional)
NOFO Number: RFA-HL-19-029
Summary:

FDA-approved medications for treating opioid use disorder are effective, but there is a significant unmet need for alternatives, especially relapse prevention. NIDA and the FDA have encouraged investigators to expand the range of therapeutic outcomes, beyond measurement of abstinence. Insomnia is a clinically significant, but understudied, correlate/predictor of relapse to substance use. Yet most medications for treating insomnia have limited efficacy and can produce side effects. The orexin (OX) system plays a key role in sleep and substance use, offering a promising avenue for study. This project will address whether OX-1/2 antagonism is a mechanism that can directly improve outpatient opioid abstinence, or whether OX antagonism corrects sleep deficiencies and indirectly improves opioid abstinence. Specific aims are to determine whether nightly treatment with the OX-1/2 antagonist suvorexant, relative to placebo, 1) increases outpatient opioid abstinence and 2) improves sleep efficiency on the residential detoxification unit. The study will also determine 3) whether improved sleep efficiency predicts greater opioid abstinence (regardless of group assignment).

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:

Current drug-screening immunoassays use benchtop analyzers that require experienced personnel, time, and a laboratory setup. Physicians without access to in-house testing have to send out patient samples for screening, resulting in unacceptable delays in the treatment of patients who are potentially suffering from chronic pain. This project, a partnership with BreviTest Technologies, LLC, aims to develop a low-cost, point-of-care (POC) urine drug testing (UDT) device to detect opioids. The goal is for a portable platform to deliver quantitative performance similar to a standard laboratory test for opioids within a 10-minute run time. If successful, this will provide a technology capable of performing rapid quantifications of urine drug levels in a physician’s office, providing an invaluable tool to render more effective pain management dosing to patients, thus paving the way toward lower toxicity and a better quality of life.

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

The Family School Partnership (FSP) and classroom-centered (CC) interventions targeted aggressive-coercive behavior and poor academic achievement as antecedents of the distal outcomes of antisocial behavior, substance abuse/dependence, psychiatric symptoms/disorders, high-risk sexual behavior and successful adaptation to the relevant developmental demands of the educational, work, romantic relationships and family (both family of procreation and origin/orientation) social fields/contexts. The participants of the FSP and CC original prevention trial were a population (n = 798) of urban, predominately African-American young adults, who began first grade in the fall of 1993 in nine elementary schools in predominantly low- to lower-middle-income Baltimore areas. The central purpose of the proposed study is to extend through ages 31-35 an examination of normal and pathogenic development and the impact of these two universal first-grade preventive interventions on the distal targets mentioned above. We will continue to study the role of phenotypic and genetic factors (and their interactions) as well as the impact of the interventions on the development and course of substance use/abuse/dependence, psychiatric symptoms/disorders, antisocial behavior/disorder and high-risk sexual behavior through young adulthood. The knowledge accrued over the course of the proposed assessments should serve to inform the nature, targets and timing of our future preventive intervention efforts.