Funded Projects

As of 2012, an infant with neonatal abstinence syndrome (NAS) was born every 25 minutes in the United States, accounting for more than $1.5 billion in national health care expenditures. These infants frequently require hospital stay in a neonatal intensive care unit (NICU), with an average hospital stay of 25 days at an average treatment cost of $66,000. Treatment of NAS usually follows a multimodal regime based on drug therapy with an oral morphine solution, mostly in combination with a sedative, but there is a need for nonpharmacological approaches. This project will test a transcutaneous auricular neurostimulation device to help NAS babies recover from opioid withdrawal without harmful side effects. The non-invasive, auricular neurostimulation device will be placed around the ear (similar to a hearing aid), and stimulation will be delivered transcutaneously.

Currently no medications are approved by the U.S. Food and Drug Administration to treat cocaine use disorder, which compromises cognitive function associated with achieving goals such as working memory, the ability to update information, and mental flexibility. This project will test whether  stimulating dopamine activity in the brain with the drug rotigotine (approved to treat Parkinson’s disease) is effective for treating cocaine use disorder. Past research has also shown that rotigotine can improve nerve cell and cognitive function in Alzheimer’s disease. This project will conduct a clinical trial to test whether treatment with rotigotine combined with cognitive behavioral therapy can reduce cocaine use in people with cocaine use disorder.

All forms of sleep deficiency can affect OUD treatment engagement and retention among people with OUD, particularly among people recently released from jail. Sleep deficiency may lead to a wide range of physical and psychological perturbations that may increase the likelihood of illicit opioid use, and disengagement in OUD treatment. This study will examine the association between sleep deficiency and OUD treatment retention in a sample of people receiving medications for OUD who were recently released from jail, to reduce morbidity and mortality from OUD among justice-involved individuals. The underlying rationale for this study is that sleep deficiency must be addressed in a holistic manner to support OUD treatment engagement. The specific aims are to 1) determine the prevalence of sleep deficiency and describe the sleep environment of a sample of people on MOUD recently released from jail; 2) estimate the association between sleep deficiency and OUD treatment retention; and 3) examine sleep environment as a potential mediator of sleep deficiency and OUD treatment retention in people recently released from jail. If successful, this study will provide data for the future development and testing of patient-centered interventions focusing on sleep deficiency among OUD treatment participants that enhance their retention in treatment

Often (around 40 percent of the time), individuals being treated for opioid use disorder (OUD) also have pain that interferes with daily life. This study builds on the prior development of a collaborative primary care approach, entitled TOPPS (Treating Opioid Patients’ Pain and Sadness), in which behavioral health specialists and primary care providers share a unified plan for addressing pain and depression in patients receiving buprenorphine. Building in preliminary work, researchers are conducting a randomized controlled trial of TOPPS compared to a health education contact-control condition among 250 persons with OUD recruited from two primary care-based buprenorphine programs, provided over 3 months and followed over 12 months. The study will examine whether this intervention changes how much pain interferes with daily functioning, the severity of pain, depression, and whether individuals stay in OUD treatment.

Low back pain (LBP) is one of the most common reasons for all physician visits in the U.S. The financial costs associated with the care of LBP are staggering. The treatments for chronic low back pain (cLBP) are far from satisfactory, and opioids are often prescribed with varying degrees of success. This study builds on prior work suggesting that auricular transcutaneous vagus nerve stimulation (tVNS), a non-invasive therapeutic, can significantly reduce symptoms of chronic pain and common comorbidities of chronic pain, such as depression and anxiety. This proposal aims to investigate the treatment effect and underlying mechanism of tVNS on chronic low back pain. Patients with chronic low back pain will be randomized to either real or sham tVNS treatment for 1 month, with a 3-month follow-up. This study, if successful, could provide new treatment options for chronic low back pain and reduce the use of opioid analgesics in chronic pain management.

Less than half of youth in the juvenile justice system who meet the criteria for substance use disorders (SUD) have ever received treatment, and less than one third of those received treatment while under community or correctional supervision. SUDs during adolescence can lead to significantly longer periods of substance use, more severe offending, and penetration in the justice system. The Translational Research on Interventions for Adolescents in the Legal System (TRIALS) cooperative is intended to develop and test implementation strategies and associated measures to improve the continuum of substance abuse and HIV prevention and treatment services delivered to youth under juvenile justice supervision.

Neonatal Opioid Withdrawal Syndrome (NOWS) is a condition that occurs when newborns are exposed to opioids during pregnancy. Symptoms often include tremors, excessive crying, sleep deprivation, and swallowing difficulties. Cases are rising, with a newborn affected by NOWS approximately every 15 minutes. Currently, healthcare providers in the United States lack standard, evidence-based treatments for NOWS. 

This project is part of a multi-center, randomized controlled clinical trial that directly compares NOWS treatments—morphine, methadone, and buprenorphine—and takes into account other types of non-drug therapies, such as behavioral interventions. The goal is to generate results that can inform clinical practice guidelines and give newborns with NOWS the best start possible. 

The University of Alabama at Birmingham routinely treats newborns with NOWS and has been part of NICHD’s Neonatal Research Network (NRN) for more than 25 years. The center has an excellent track record of enrollment in clinical studies, with successful follow-up to 2 years of age and beyond.

The parent U19, “Southwest Hub for American Indian Youth Suicide Prevention,” builds capacity among local tribal governments, investigators, interventionists, and service providers across three Southwestern states to: 1) identify at-risk youth and gather robust local data through surveillance; 2) provide regular monitoring and brief interventions to close gaps in continuity of care; and 3) convene regularly for shared learning, policy development, and dissemination of best practices. The parent U19 includes an innovative SMART trial study design. The purpose of this supplement is to gather data on opioid use. Our supplement aims are to: 1) expand suicide surveillance in the Southwest Hub to include opioid use as a potential precipitant, facilitator, and risk factor for subsequent suicidal behavior; 2) explore community beliefs about correlates of risk, protective factors, and behavior functions of opioid abuse in Native American youth; and 3) examine opioid use among SMART trial participants.

Opioid use disorder, a chronic and relapsing disease, is a significant and escalating public health concern. But, despite the availability of approved pharmacotherapies and promising therapeutic interventions, the high rates of relapse indicate a critical need for a better understanding of the factors that contribute to relapse to opioids, and for the development of new treatment approaches. Sleep problems are a common symptom in most substance use disorder syndromes, including opioid use disorder (OUD), but they are severely undertreated, partly because the standard hypnotic medications used to treat sleep disorders are themselves addictive. This study will investigate whether activating the glucagon-like peptide-1 receptor pathway can help reduce craving while improving sleep in OUD patients. The FDA-approved medication liraglutide, a GLP-1R agonist, is currently approved to treat Type II diabetes mellitus and obesity in humans. This proposal for a supplemental study will add polysomnography, the gold-standard for evaluating sleep architecture, to an ongoing study. If successful, this study will provide a strong rationale for conducting a full multi-site, Phase III clinical trial.

This project will use a data-to-action framework to guide implementation of opioid use disorder treatment and harm reduction interventions based on rapid data analysis. It will leverage existing data systems such as Emergency Medical Services (EMS) reports, mobile integrated health case management data, and medical examiner data for near real-time data analyses, visualization, and action planning. This research will collect a range of data (opioid treatment, use of acute care services, morbidity, mortality, incarceration, housing support, and cost benefits) from a sub-acute stabilization center for people at high risk for opioid overdose, including those who have recently overdosed and are referred and transported by EMS teams.

Adolescents and young adults in justice settings (AYAJS) have some of the highest rates of opioid use disorder (OUD), with national rates approaching 20%. Multiple studies have established effectiveness of the Adolescent Community Reinforcement Approach with Assertive Continuing Care (ACRA/ACC) in reducing non-opioid substance use disorder (SUD); however, none have evaluated it as an OUD prevention strategy. SUD is common and costly among AYAJS; thus, ACRA/ACC-based approaches are likely to be effective and cost-beneficial OUD prevention strategies for this group. However, the optimal intensity of an ACRA/ACC-based OUD prevention intervention for AYAJS with and without non-opioid SUD is not known, as these groups are likely to have differing prevention needs. Seattle Children’s Hospital (SCH), University of Washington (UW), and Washington State Juvenile Rehabilitation (WSJR) will collaboratively evaluate ACRA/ACC-based OUD prevention strategies of different intensity levels among SUD and non-SUD youth.

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.

Community pharmacies are optimal—yet underutilized—settings for identifying individuals with opioid use disorder (OUD) and increasing their access to treatment. Approximately 93 percent of individuals in the U.S. live within 5 miles of a community pharmacy. The most common opioid-related tool available to pharmacists is the prescription drug monitoring program (PDMP), which provides highly limited information and support for clinical decision making. Appriss Health, the largest U.S. PDMP vendor, covering 42 states, has developed an opioid risk measure, the NarxScore. This study will clinically validate the NarxScore metric and identify high, moderate and low opioid risk thresholds to inform OUD care management within urban and rural community pharmacies. This is a prospective cross-sectional comprehensive OUD risk and behavioral/physical health survey administered electronically with patients (n = 1,523) filling opioid medications in urban/rural community pharmacies in Ohio (pharmacy sites: n = 12) and Indiana (pharmacy sites: n = 3), states that continue to have disproportionately high rates of overdose and opioid prescribing. Correlation, regression and kappa statistics will be calculated for validation; receiver operating curves with sensitivity/specificity values will be employed for threshold identification (with >95 percent power to detect an area of 0.7 under the curve value).