Funded Projects

NOFO Title: NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Required)
NOFO Number: PA-18-344
Summary:

Chronic pain is a significant public health problem associated with tremendous personal and economic burden. First-line treatment consists of opioid medications, but despite only moderate efficacy and unpleasant side effects, rates of opioid prescriptions have quadrupled over the past 15 years, and this has contributed to high rates of misuse, overdose, and mortality. Clearly, alternative, or non-opioid strategies for treating pain are needed. In this context, “opioid-sparing” medications refer to compounds that can be combined with and enhance the analgesic effects of lower-dose opioids without increasing the rewarding properties of either drug. There is preclinical evidence suggesting that cannabidiol (CBD) may have the potential to function as “opioid-sparing” medications, but its ability to alter opioid-mediated analgesia in humans has yet to be determined. This proposal will fill this gap by conducting a double-blind, placebo-controlled, within-subject randomized crossover study of the effects of CBD and morphine co-administration on pain sensitivity and subjective reinforcement on 28 healthy males and females. This is the first known study to investigate the ability of CBD to alter morphine’s analgesic effects in humans. If successful, the model will have a lasting impact on our ability to develop and test medications that reduce our reliance on chronic use of opioid medications for pain relief.

NOFO Title: Research Project Grant (Parent R01)
NOFO Number: PA-13-302

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 United States has seen dramatic increases in fatal overdoses due to heroin, counterfeit prescription drugs, and cocaine adulterated with fentanyl or fentanyl-like analogs. Current medications may not be sufficient to address the opioid overdose epidemic. As a complementary strategy, the researchers plan to develop vaccines against fentanyl and fentanyl-like compounds to reduce their abuse liability and the growing incidence of fatal overdoses. This research team has already developed vaccines against heroin and oxycodone that stimulate the production of antibodies effective in reducing opioid distribution to the brain, opioid-induced behaviors, and opioid-induced respiratory depression and have identified a promising fentanyl vaccine candidate cued up for optimization. Successful completion of an anti-fentanyl vaccine development project could offer a long-lasting, safe, and cost-effective intervention complementary to medication-assisted treatment (MAT) and may reduce overdoses in opioid users as well as protect people in professions (e.g., law enforcement, airport security, postal workers) at risk of accidental exposure to fentanyl and fentanyl analogs.

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

Emergency department (ED)-initiated buprenorphine/naloxone (BUP) with referral for ongoing BUP is superior to referral alone in engaging patients with untreated opioid use disorder (OUD) in treatment at 30 days and is cost-effective. However, logistical barriers exist in translating research into practice. New BUP formulations such as the extended-release injectable BUP (CAM2038, XR-BUP) hold promise in addressing many of the barriers more effectively than sublingual buprenorphine (SL-BUP) by treating the patients’ symptoms for up to seven days. This study will recruit, train and provide resources to 30 ED sites throughout the U.S. using implementation facilitation strategies to address stigma and provide ED-initiated BUP for patients presenting with OUD who are not receiving medications for OUD. Once implementation is adequately achieved, the sites will conduct a randomized controlled trial (RCT) to compare the effectiveness of SL-BUP versus XR-BUP on ED patients’ engagement in formal addiction treatment seven days after their ED visit. In addition, in an ancillary component of the study, the use of XR-BUP will be assessed in ED patients with Clinical Opioid Withdrawal Scale (COWS) scores of

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:

Chronic pain and opioid use disorders (OUD) are burgeoning interrelated epidemics. Sleep disturbances are prevalent, treatable, and increasingly recognized as risk factors for both chronic pain and OUD. Sleep disruption impairs endogenous pain inhibition, linked to analgesic efficacy and rewarding properties of mu-opioid receptor (MOR) agonists. It is not known, however, whether sleep disturbance causally alters mechanisms that contribute to OUD risk. Sleep continuity disruption (SCD) and/or sleep fragmentation (SF) may alter cerebral MOR availability, and these forms of sleep disruption may increase OUD risk. This study aims to 1) evaluate whether experimental SCD and/or SF alter resting or pain-evoked MOR binding potential (BP) in brain regions associated with pain inhibition; 2) examine whether SCD and/or SF alters the analgesic response; and 3) determine whether MOR BP in brain regions of interest are associated with analgesia and abuse liability.

NOFO Title: Grand Opportunity in Medications Development for Substance-Use Disorders (U01 Clinical Trial Optional)
NOFO Number: PAR-18-219
Summary:

There are no FDA-approved medications for stimulant use disorders, and therapies for opioid use disorders remain suboptimal in ways that are now a focus of national attention. Thus, there is a clear need to identify new targets and explore new approaches for addiction medication development. Several lines of evidence suggest that PTPRD (receptor type protein tyrosine phosphatase D) may be a promising target for development of pharmacotherapeutics to treat not only stimulant use disorders but opioid use disorders as well. This research will focus on improving existing PTPRD ligands, identifying their effects on the dopamine and opioid systems, and moving the best novel, patentable PTPRD ligands toward human studies. If successful, this project will generate novel, well-tolerated, and bioavailable PTPRD ligands that display in vitro potency, selectivity and stability, and in vivo modulation of both cocaine and opioid-mediated reward at doses that present no significant toxicity.

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:

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: 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:

With the entwined crises of opioid use and chronic pain, there is a need for alternative, safe therapies to manage opioid use disorder, opioid withdrawal symptoms, chronic pain, and/or associated anxiety and depression. A proof-of-concept preclinical study has already been conducted of a cannabinoid-opioid combination that demonstrated opioid-sparing and synergistic analgesic effects, with the combination providing greater analgesia in a rodent model of chronic pain than a standard dose of the opioid alone. This proposal aims to develop a fixed-dose combination (FDC) of the cannabinoid-opioid that may have improved analgesia with lower opioid doses and thereby lower the risk of dependence, withdrawal, diversion, abuse, and overdose. Preclinical pharmacokinetic and ?in vivo ?safety studies will help determine if co-administration alters the pharmacokinetics and/or respiratory depression related to either compound in rodents.

NOFO Title: Data Coordinating Center for the NICHD Neonatal Research Network (U24)
NOFO Number: RFA-HD-18-010
Summary:

The ACT NOW Eat, Sleep, Console (ESC) Clinical Trial approach to the management of neonatal opioid withdrawal syndrome (NOWS) emphasizes parental involvement, simplifies the assessment of infants with NOWS and focuses interventions on non-pharmacologic therapies. Although outcomes following implementation of the ESC care approach, inclusive of the ESC Care Tool, appear promising and initial accounts suggest that it is safe, there has yet to be a rigorous randomized clinical trial to demonstrate the safety, efficacy and generalizability of its use in the care of infants with NOWS. The ESC Clinical Trial leverages the infrastructure and collaborations of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network and the IDeA States Pediatric Clinical Trials Network to reach the populations most affected by the opioid epidemic. The trial will provide answers to numerous critical gaps in our knowledge with respect to the best practices for the identification and management of infants with NOWS, as well as our understanding of the outcomes of these infants.

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:

Rates of neonatal abstinence syndrome have reached a staggering 6.5 per 1,000 births nationwide, creating an urgent need to identify how in-utero exposure to opioids and associated risk factors influence the developing brain. A multidisciplinary team will address these challenges in Oregon, a state particularly hard hit by the opioid epidemic. Through linking sites, the impact of the Phase I project is enhanced and will provide critical information to support a national-level effort for Phase II of the HEALthy Brain and Child Development Study. Aim 1 will develop, implement, and evaluate innovative recruitment and retention strategies for high-risk populations. Aim 2 will address anticipated challenges of the planned Phase II study by implementing and evaluating a multi-site, standardized research protocol including multimodal MRI of placenta, fetus, neonate, and 24-month-old brain; biospecimen collection; and assessment of substance use and other key domains. Aim 3 will evaluate data acquisition, processing, and statistical considerations to maximize data quality, usability, and integration across 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:

High relapse rates among people with opioid use disorder (OUD) indicate that addiction involves appetitive pathways. Peripheral stimulation of the glucagon-like peptide-1 receptor (GLP-1R) “satiety” pathway could reduce heroin seeking and taking. Pretreatment with a GLP-1R agonist reduces heroin taking, seeking, and drug-induced reinstatement in rats. This project tests whether GLP-1R agonists can reduce relapse in humans with OUD. A pilot study will be conducted to determine whether once-daily treatment with the shorter acting GLP-1R agonist, liraglutide, can safely and effectively reduce cravings among OUD patients. Animal models will be used to test the efficacy and safety of a longer-acting GLP-1R agonist, semaglutide, and then a clinical trial will be conducted to test whether semaglutide will reduce relapse and use in animal models. If successful, the study will show that treatment with GLP-1R agonists can safely and effectively reduce opioid craving, seeking, and relapse.

NOFO Title: Clinical Trials or Observational Studies of Behavioral Interventions for Prevention of Opioid Use Disorder or Adjunct to Medication Assisted Treatment-SAMHSA Opioid STR Grants (R21/R33)
NOFO Number: RFA-AT-18-002