Funded Projects

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 Louisville serves a large, diverse population that is disproportionately affected by the opioid crisis. Mothers and infants treated by the university’s healthcare team live in rural
and urban underserved regions where the frequency of opioid use during pregnancy is among the highest in the country, with a rate estimated at 3 times the national average.

Neonatal opioid withdrawal syndrome (NOWS) has emerged as a tragic by-product of the opioid epidemic. Newborns whose mothers used opioids while pregnant can experience symptoms of opioid withdrawal in the days following birth, such as tremors, irritability, seizures, sleep, digestive, and feeding problems. However, little is known about the effect of antenatal opioid exposure on longer-term infant development over time. To address this gap in understanding, the ACT NOW Longitudinal study is examining a crucial developmental period from birth to two years of life through a comprehensive battery of assessments, including MRI imaging, neurodevelopmental behavioral assessments, and family report measures. This longitudinal cohort study is projected to include a total of 375 infants, 250 who were exposed to opioids and 125 matched controls.

Many millions of Americans experience chronic pain, including about 25 million who report pain that substantially interferes with daily activities and reduces quality of life. Many chronic pain syndromes are more prevalent in females, and the incidence of chronic pain increases dramatically during adolescence. This research will use neuroimaging and other biological, social, and psychological data from a large study of young adolescents with or without pain to identify risk and protective factors for chronic pain.

The study team developed an mHealth pain self-management intervention for the perioperative period (SurgeryPal) to target psychosocial risk factors and teach pain self-management skills. The goal of this proposal is to establish the effectiveness of the SurgeryPal psychosocial intervention to improve clinically meaningful outcomes in adolescents undergoing major musculoskeletal surgery, and to identify the optimal timing of intervention delivery. The study team will plan for the efficient implementation of a multisite randomized clinical trial at 25 centers in 500 youth ages 12–18 years undergoing spinal fusion surgery and their parents. Participants will be randomized to receive SurgeryPal or attention control condition during the preoperative and postoperative phases. Self-reported pain severity and interference and secondary outcomes will be assessed at baseline, 3-, and 6-months. If effective, this scalable, low cost intervention will allow broad implementation to prevent chronic postsurgical pain in youth.

Chronic pelvic pain affects social and sexual quality of life in up to 20% of women in the United States. It is often managed with physical therapy approaches, but when these measures fail, injection therapies may be indicated. These include injection of botulinum neurotoxin, which leads to muscle relaxation in the pelvic floor and thus pain relief. However, botulinum neurotoxin has dose-dependent side effects and is expensive. Therefore, a precision injection technique to administer botulinum neurotoxin so that it remains effective while minimizing adverse effects and costs is needed. Hillmed Inc. has developed a technique to assess the pelvic floor and choose the optimal injection site, which has improved treatment outcome in initial analyses. They are now aiming to develop a commercializable, personalized precision injection medical device for botulinum toxin and software package that will enable clinicians to optimize botulinum neurotoxin injection. They will then assess the system’s efficacy in a clinical trial of women with chronic pelvic pain and healthy women.

To tackle the national public health emergency posed by opioid misuse, addiction, and overdose deaths, the development of effective new medications and the FDA drug approval process must be accelerated. In response to this call, INSYS Development Company, Inc. (INSYS) has developed a cannabidiol (CBD) oral solution that shows promise as a novel medication for prevention of relapse that addresses one of the five opportunities specified in the HEAL Initiative to improve treatment options. The first phase of this project involves clinical trials of CBD on cue-induced cravings, modulation of withdrawal, alterations of negative affect states, relapse to opioid use, and treatment retention in patients with OUD receiving buprenorphine treatment in a residential drug treatment facility. The findings from this phase will inform further studies in an outpatient setting. If successful, this project could advance to the development of a new monotherapy for the treatment of OUD.

This project creates the HEAL Data2Action Data Infrastructure Support Center that will conduct research as well as support the HEAL Data2Action Innovation Projects with analytics and support for navigating electronic health records and other “big data” sources, as well as logistical processes related to privacy and ethics. The center will help plan for data collection and assessing outcomes, as well as provide data visualization efforts for various stakeholders. Key support mechanisms include courses, seminars, conferences, trainings, and on-demand technical assistance.

The HEALthy Brain and Child Development National Consortium (HBCD-NC) will establish a normative model of developmental trajectories over the first 10 years of life. All sites in the HBCD-NC will carry out a common research protocol and will assemble and distribute a comprehensive and well curated research dataset to the scientific community at large. The HBCD-NC will collect neural, behavioral, physiological, and psychological measures, as well as biospecimens, to characterize neurodevelopmental trajectories. Most participants will be recruited in the second trimester of pregnancy, with a smaller subset recruited at birth, and followed for the first 10 years of life. The Children’s Hospital of Los Angeles study site will enroll participants from across the Greater Los Angeles region, where the prevalence of legal and illegal non-opioid drug use is high, enabling researchers to recruit from diverse, high-risk populations.

Deaths from opioid overdose are highly preventable with early detection and administration of naloxone, but overdose victims often die because they are alone or among untrained or impaired bystanders and thus do not receive timely resuscitation. There is an urgent, unmet need for a low-barrier, easily scalable solution that can identify opioid overdoses in real time and rapidly connect victims to naloxone therapy. This proposal seeks to commercialize an innovative overdose detection software product that can be downloaded on any commodity smartphone and can detect opioid- induced respiratory failure (i.e., overdose) and summon help. The software-only product, SecondChance, converts a smartphone into a short-range active sonar system capable of monitoring breathing and detecting overdose.

Although medication-based treatment for opioid use disorder (OUD) can effectively reduce overdose risk and improve health outcomes, most people discontinue treatment too soon. Peer support specialists, who are individuals with direct experience with a substance use disorder, can offer social support to help individuals with OUD overcome barriers to treatment and recovery. This project will develop, deliver, and evaluate an innovative peer support specialist intervention to help individuals begin and stay in a treatment program. The research will focus on rural populations and underserved communities, using a dynamic modeling framework to prioritize at-risk communities for treatment offered through mobile health clinics.

Increasing primary care clinician intention and behavior to obtain waivers to prescribe buprenorphine for treatment of opioid use disorder and increase use of the Opioid Wizard, a clinical decision support tool, has potential for patient benefit. This supplement will provide support to evaluate a training tool as an intervention to reduce stigma in primary care clinics by integrating a stigma reduction training component into the Opioid Wizard training at multiple sites of the NIDA Clinical Trial Network. Primary care providers will be randomized to novel stigma reduction training, grounded in stigma science, or an attention-control training to determine whether stigma reduction training reduces provider stigma, increases intention to apply for a waiver to prescribe buprenorphine, and ultimately increase the likelihood that providers use Opioid Wizard. The proposed supplement will utilize the randomized controlled trial design embedded in the larger multisite trial to evaluate the Opioid Wizard tool to help primary care clinicians identify, diagnose, and treat patients with opioid use disorder while evaluating the effect of the stigma reduction training.

In collaboration with Eolas Therapeutics and the NIH Blueprint Neurotherapeutics Network, AstraZeneca has developed a novel compound for treatment of opioid use disorder, AZD4041, which targets orexin 1 (OX1) receptors in the brain. In animal studies, AZD4041 reduced the motivation to consume opioids or nicotine, reduced relapse-like drug-seeking behaviors, and showed a favorable safety profile. The compound also has proven to be safe in an initial Phase 1 clinical trial in healthy human volunteers. This project will further evaluate the safety (e.g., respiratory depression profile) of AZD4041 in human volunteers, using multiple and increasing doses. Upon successful completion of these studies, the compound will be tested in a proof-of-concept efficacy study in patients with opioid use disorder. If this is successful, the compound will advance to larger Phase 2 and Phase 3 pivotal clinical trial to tests its effectiveness in the treatment of opioid use disorder.