Funded Projects

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

Over-the-counter medicines such as non-steroidal anti-inflammatory drugs are ineffective for treating severe chronic pain and may have serious side effects from continued use, which limits treatment options. A kinase (an enzyme whose activity targets a specific molecule) called TAK1 is involved in the chronic pain process. This research will develop a molecule previously shown to be effective in a model of inflammatory pain that also inhibits TAK1. A main goal will be to determine if this inhibitor (takinib analog HS-276) can cross the blood-brain barrier and, if successful, pursue FDA  Investigative New Drug-enabling safety studies leading to a Phase I clinical trial and a potential new chronic pain treatment.

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:

For individuals with moderate to severe opioid use disorder (OUD), medication-assisted treatments (MATs) such as oral methadone and extended-release naltrexone (XR-NTX) are the gold standard in initiating and maintaining long-term recovery. Still, many patients struggle with persistent sleep disturbance and stress reactivity in the early stages of recovery, which drive relapse behaviors. This proposal constitutes a novel mechanistic approach to understanding the role of the orexin system in sleep disturbance and circadian rhythms of stress in OUD patients who are maintained on MATs and are early in recovery. This study will determine whether the FDA-approved sleep medication suvorexant (SUVO) improves sleep continuity and decreases diurnal measures of stress, and whether improvement of sleep/stress processes translates to improved OUD treatment outcomes. Its findings will fill critical gaps in our understanding of the role of the orexin system in sleep disturbance and circadian rhythms of stress that impact OUD recovery.

NOFO Title: NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)
NOFO Number: PA-18-484
Summary:

Opioids remain the gold standard for treating moderate to severe pain, but their use is limited by numerous adverse effects, including tolerance, dependence, abuse, and overdose. Adverse effects could be avoided by combining an opioid with another drug, such that smaller doses of the opioid (in combination with another drug) produce the desired therapeutic effect. Direct-acting serotonin type 2 (5-HT2) receptor agonists interact in a synergistic manner with the opioid morphine to produce antinociceptive effects, suggesting a 5-HT2 receptor agonist could be combined with small amounts of an opioid to treat pain, thereby lowering the risk associated with larger doses. Unfortunately, very little is known about interactions between 5-HT2 receptor agonists and other opioids. The proposed studies will evaluate the therapeutic potential of mixtures of opioids and 5-HT2 receptor agonists using highly translatable and well-established procedures to characterize the antinociceptive, respiratory-depressant (overdose), positive-reinforcing (leading to misuse), and discriminative-stimulus (subjective) effects of drug mixtures as well as the impact of chronic treatment on the development of tolerance to and physical dependence on opioids. If successful, these studies will provide proof-of-concept for this innovative approach to pain treatment and evaluate the utility of targeting 5-HT receptors for analgesic drug development.

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:

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: Advancing Validated Drug Targets for Substance Use Disorders (R43/R44 - Clinical Trial Not Allowed)
NOFO Number: RFA-DA-22-023
Summary:

New and safe therapeutic targets for treating opioid use disorder are needed. One promising approach is to test drugs currently approved by the U.S. Food and Drug Administration that work independently of the body’s opioid system. The medication memantine targets N-methyl-D-aspartate (NMDA) receptors in the brain, which have been implicated in the development and maintenance of addiction. This project will study a miniature version of multiple memantine molecules bound together that attaches only to NMDA receptors that are not within nerve connections. The research will evaluate the safety, misuse potential, and effectiveness of this molecular assembly in preclinical models. 

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:

Patients with chronic low back pain, often have depressive and anxiety symptoms and use opioids all of which are associated with stigma. In turn stigma leads to decreased treatment seeking and adherence, increased depression and pain, and poor treatment outcomes. Intersection of these health-related stigmas may have synergistic effects. This study aims to enhance the findings of a clinical trial to test antidepressant medication and Enhanced Fear Avoidance Rehabilitation in patients with chronic low back pain and high levels of depression and anxiety. The effects of these intersecting types of stigma on the efficacy of the interventions will be evaluated to better understand the needs of the patient population and to inform development of a stigma reducing intervention that can be implemented care providers.

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; PA-21-071
Summary:

Effective treatments for opioid use disorder need to address the complex needs of patients, which may include mental health problems and substantial chronic pain. This project will measure lifetime trauma experienced by men and women who take medication for opioid use disorder, as well analyze the association between types of trauma and symptomatic distress. The project will also explore whether an individual’s perceptions of sensations from inside their body (interoceptive awareness) affect emotional control and mental health. This research will fill knowledge gaps i critical to better understanding opioid use disorder treatment and relapse.

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

Hospital inpatient stays due to opioid-related health problems are a reachable moment for increasing access to treatment with medications for opioid use disorder (MOUD). Hospitalized patients with opioid use disorder (OUD) are at particularly high risk for morbidity, mortality, and high medical costs in the U.S. This study will substantially inform the care management of OUD in hospitalized patients. The project includes a comparative effectiveness research trial and an implementation research trial, which will lead to models of broad dissemination for treatment approaches to this largely unaddressed population. They will examine whether (1) in hospitals with addiction medicine consultation services, hospital-initiated extended-release buprenorphine (XR-BUP), compared with other OUD medications, results in increased engagement in treatment with MOUD following hospital discharge and (2) training hospitals without such consultation services on best practices for initiating MOUD using consultation service hubs improves medication uptake in hospitals and increased MOUD treatment engagement following discharge.

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

Hospital inpatient stays due to opioid-related health problems are a reachable moment for increasing access to treatment with medications for opioid use disorder (MOUD). Hospitalized patients with opioid use disorder (OUD) are at particularly high risk for morbidity, mortality, and high medical costs in the U.S. This study will substantially inform the care management of OUD in hospitalized patients. The project includes a comparative effectiveness research trial and an implementation research trial, which will lead to models of broad dissemination for treatment approaches to this largely unaddressed population. They will examine whether (1) in hospitals with addiction medicine consultation services, hospital-initiated extended-release buprenorphine (XR-BUP), compared with other OUD medications, results in increased engagement in treatment with MOUD following hospital discharge and (2) training hospitals without such consultation services on best practices for initiating MOUD using consultation service hubs improves medication uptake in hospitals and increased MOUD treatment engagement following discharge.

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:

Harm reduction supplies include fentanyl test strips that allow people who use drugs to identify whether the substance(s) they plan to take contain fentanyl and sterile syringes that help to prevent the spread of infectious diseases among people who inject drugs. One potential way to increase access to harm reduction supplies is mail delivery. This project will describe state-level policies that deter the use of mail-based delivery of harm reduction services, examine characteristics of people who use mail-based harm reduction services, and assess individual preferences related to mail-based harm reduction services.

NOFO Title: Limited Competition: International Cooperative Biodiversity Groups (U19)
NOFO Number: RFA-TW-13-001
Summary:

This International Cooperative Biodiversity Group application aims to discover and develop small molecule drug leads from cultured marine microbes and diverse coral reef organisms collected from Fiji and the Solomon Islands. Drug discovery efforts will focus on four major disease areas of relevance to the United States and low- and middle-income countries: infectious disease, including tuberculosis and drug-resistant pathogens; neglected tropical diseases, including hookworms and roundworms; cancer; and neurodegenerative and central nervous system disorders. Screening in these therapeutic areas will be performed in collaboration with two major pharmaceutical companies, two highly respected academic groups, and various testing centers and government resources that are available to facilitate drug discovery and development. The acquisition of source material for this program will be linked to biotic surveys, informed by ecological investigations addressing the chemical mediation of biotic interactions, and enriched using ecology-based strategies designed to maximize secondary metabolite production and detection.

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
Summary:

This proposal aims to test the impact of an empirically derived implementation strategy—under real-world conditions and across multiple child service systems—on successful adoption and sustainment of two evidence-based programs that address adolescent substance abuse: Treatment Foster Care Oregon (TFCO; formerly Multidimensional Treatment Foster Care) and Multidimensional Family Therapy (MDFT). The overarching goal of this proposal is to evaluate whether the integration of implementation fidelity (fidelity to the implementation process) with intervention fidelity (fidelity to the clinical intervention) can increase the probability that a new organizational site not only successfully adopts a program but develops the infrastructure to ensure it can sustain. This study will (a) evaluate the effect of stages of implementation completion coaching strategy (SIC-CS) on outcomes of program adoption and sustainment, (b) extend the SIC to include measurement of sustainment, and (c) examine cost and resource patterns most likely to yield sustainable programs.