Funded Projects

A recent FDA public meeting identified sleep disturbance as a primary contributor to opioid use disorder (OUD) treatment failure. Suvorexant (SUVO; Belsomra®) is a dual orexin receptor antagonist that is FDA-approved for insomnia, with low addiction liability, that improves sleep continuity with a single dose, has an extremely safe and mild side-effect profile, has clear interactions with the opioid system, and has not yet been evaluated in OUD patients. The hypothesis is that SUVO will improve total sleep time during withdrawal, have no addiction liability, and be more efficacious than trazodone, a common OUD-associated insomnia medication. Primary outcomes will be objective sleep measures and addiction liability. Secondary measures will include objective, biological, and self-report measures of opioid withdrawal severity, treatment retention, craving, and stress. Results will advance the treatment of OUD, the understanding of sleep and opioids, and the use of SUVO in clinical populations.

NIH is supporting the Justice Community Opioid Innovation Network (JCOIN), a collaboration of justice and behavioral health stakeholders that will study approaches to increase high-quality care for people with opioid misuse and opioid use disorder in justice populations. This multi-site clinical research center aims to improve local community public health and safety outcomes for reentering justice- involved individuals who have a history of (or are at risk for) using opioids by comparing two implementation strategies and two interventions at the client and system levels. The study will also examine which implementation strategy is most effective for increasing service linkage and initiation, services retention, and improved opioid-related public health safety outcomes.

For many reasons, the emergency department (ED) is a critical venue to initiate opioid use disorder (OUD) interventions. ED patients have a disproportionately high prevalence of substance use disorders and are at an elevated risk of overdose, and many do not access health care elsewhere. Despite this, OUD interventions are rarely initiated in EDs. The Emergency Department Connection to Care with Buprenorphine for Opioid Use Disorder study (CTN-0079) will assess the feasibility, acceptability and impact of introducing clinical protocols for screening for OUD, buprenorphine treatment initiation, and referral for ongoing treatment in ED settings with high need, limited resources and different staffing structures. This extension study will use the existing infrastructure to evaluate the adoption and sustainability of the clinical protocols introduced at each of the study sites and to identify factors influencing their diffusion and effectiveness.

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.

Many individuals with opioid use disorder (OUD) pass through the criminal justice system over the course of their life. Improved access to high-quality, evidence-based addiction treatment in justice settings will be critical to addressing the opioid crisis. Through the Justice Community Opioid Innovation Network (JCOIN), the National Institutes of Health will study approaches to increase high-quality care for people with opioid misuse and OUD in justice populations. The Methodology and Advanced Analytics Resource Center (MAARC) will provide data infrastructure support across the network using advanced methods that provide best-in-class data storage, management and security with added value to clinical trials through products of forecasting, rapid real-time assessments, explication and exploration of trial findings, and cost-effectiveness analysis.

This training and dissemination project will develop an office-based buprenorphine treatment module for primary care, including the algorithm for buprenorphine treatment and integration of OUD measures; assess the acceptability of the OUD module; evaluate the impact of the OUD module on screening and identification rates of problem opioid use and successful initiation and maintenance rates of buprenorphine in primary care; assess barriers to implementation of buprenorphine treatment and methods for overcoming these barriers in the network partner clinics; and develop a strategy to refine and more broadly implement opioid problem use and OUD treatment.

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

The opioid crisis continues its highly negative impact, with more than 49,000 opioid-related overdose deaths in 2017. In 2016, the Centers for Disease Control and Prevention (CDC) issued guidelines for opioid prescribing that included opioid dosing and risk mitigation strategies, and health systems implemented similar initiatives even earlier. This has resulted in a quickly changing and more conservative prescribing environment. National data indicate the number of prescriptions has fallen between 2013 and 2016. Registries and electronic health record (EHR) data are increasingly cited as valuable resources to address critical research questions on opioid use with high efficiency. To our knowledge, no investigators have established an EHR-based prescription opioid registry across several diverse health systems with common data algorithms with the flexibility to address multiple questions. The goal of the proposed research is to develop a prescription opioid registry across 10 diverse health systems with harmonized EHR data from years 2012-2018 and leverage it to answer several key “next-step” research questions in response to the opioid crisis. The registry will include medications prescribed for treatment of OUD, including buprenorphine products.

Expanding access to naloxone in the community through the pharmacy can be a critical mechanism for extending this lifesaving medication’s reach. This study will partner with two large retail pharmacy chains and integrate two interventions that provide knowledge and training for pharmacists to identify and effectively engage with patients who may be at high risk for an opioid overdose. The interventions will be combined into a cohesive educational program, implemented in 160 community pharmacies and tested for effectiveness. Study findings will create a generalizable, evidence-based training and toolkit for pharmacists caring for patients who use prescribed or illicit opioids, in more than 40 states adopting or expanding pharmacy naloxone.

There are alarming rates of substance abuse and diversion in hospitals, with multiple studies finding that roughly 10% of our nation’s nurses, anesthesiologists, and pharmacists are currently diverting drugs in their workplaces. Diversion continues even though most hospitals already lock addictive drugs in Automated Dispensing Machines (ADMs) and run monthly “anomalous usage” computer reports to try to detect diversion. This SBIR project will research mechanisms to detect when health care workers (HCWs) in hospitals steal or “divert” legal drugs, either to abuse themselves or to illegally sell to others, by building a computer system with (a) automated data feeds from multiple existing hospital computer systems and (b) advanced analytics to flag potential diversion for investigation. This research has the potential to reduce injuries to HCWs who are becoming addicted, destroying their careers, jeopardizing their patients’ safety, and increasingly dying from drug diversion overdoses.

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.