Funded Projects

The HEALthy Brain and Child Development National Consortium (HBCD-NC) will establish a normative template 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. The majority of participants will be recruited in the second trimester of pregnancy, with a smaller subset recruited at birth, and followed for the first decade of life. The University of Vermont study site will recruit mother-infant dyads from a rural area in Vermont, a state in which nearly one-third of neonatal hospitalizations are for neonatal abstinence syndrome (NAS).

This research will expand the understanding of the effects of non-invasive vagal nerve stimulation on patients with opioid use disorder by examining the relationship between nerve stimulation and treatment, respiratory physiology, withdrawal symptoms, and relapse. Additionally, these relationships will be added to existing algorithms and equipment being developed by the Inan Research Lab at the Georgia Institute of Technology. Collecting and determining the quality of conventional respiration signals, as well as collecting high-resolution impedance based respiratory measurements, will help to determine the impact of non-invasive vagal nerve stimulation on breathing and lung function in people with opioid use disorder, toward development of a profile of physiological effects of non-invasive vagal nerve stimulation during opioid withdrawal.

Migraines and other headaches are often debilitating for patients, yet few treatment options providing sustained relief exist. All available therapies, including frequently prescribed opioids, have considerable side effects or limitations. Therefore, novel treatment approaches are needed to reduce or eliminate the need to use opiates and other systemic pharmaceuticals. Thermaquil Inc. has developed a new way of stopping migraine and other headache pain by noninvasively blocking pain signal transmission in the head, which in initial studies allowed patients to discontinue use of opioids and other addictive pain medications. Thermaquil will now be conducting a larger randomized controlled trial to demonstrate the safety and effectiveness of this novel approach. After a baseline period, patients will be randomly assigned to the active or control condition and receive a single treatment. The study will continue for 12 weeks with the active versus control arms, before all patients will be given active therapy for an additional 12 weeks.

There are a dearth of integrated treatments that simultaneously address the fundamental causes of chronic pain and opioid misuse/opioid use disorder and that focus on well-being among individuals with chronic pain and opioid misuse/disorder. This research will study how to improve the lives of patients with chronic pain and opioid misuse/disorder via tailored interventions that explicitly target increasing quality of life and engagement in valued activities, the cultural centering of interventions to meet the needs of diverse patient populations and reducing stigma of chronic pain and opioid misuse/disorder. Specific research projects will i) test the effectiveness, mechanisms, and implementation of an integrated psychosocial treatment for chronic pain and opioid use disorder among individuals receiving buprenorphine from outpatient treatment clinics, and ii) will use community-based participatory research methods to develop a culturally centered strategy for screening and brief intervention of chronic pain and opioid use disorder among American Indian/Alaska Native patients in primary care settings. This research will shed light on a difficult problem and improve health and wellbeing with a focus on diverse and underserved populations.

Opioid use and addiction affects more than 2 million Americans and contribute to a large proportion of all drug overdose deaths. Current treatments for opioid use disorder (e.g., methadone and buprenorphine) are not always effective, may be misused, and can have side effects that discourage treatment continuation. Therefore, Cerevel Therapeutics is evaluating a novel compound, CVL-936, which targets brain molecules called dopamine D3 receptors. These receptors are involved in the brain’s reward and relapse pathways and are present in higher levels in people with addictions. In animal studies, the molecule reduced self-administration of nicotine and fentanyl, including in relapse situations. The project will test the safety and tolerability of CVL-936 in animals and healthy humans and will examine its effectiveness in reducing craving in people with opioid use disorder.

Chronic low back pain affects millions of Americans and is difficult to treat. Currently, there are no reliable methods to determine the best treatment options for patients, or to objectively evaluate the effectiveness of various interventions. This research will develop an imaging technology that uses machine learning to make automated assessments of spine characteristics, pain response, and patient-reported outcomes in people with chronic low back pain. This award will be used to recruit and support two postdoctoral fellows from populations underrepresented in biomedicine. The research will focus on whether use of the imaging tool helps clarify clinical diagnoses, as measured by the level of agreement between radiologists before and after using the tool.

There is an urgent need for non-opioid post-operative pain management solutions.  This research is developing a naturally absorbable polymer film that can release controlled amounts of the non-opioid analgesic bupivacaine – aiming to manage pain for several days following surgery. Project objectives are to optimize the timing of drug release, develop manufacturing standards, determine effective dosage for preserving motor function, and determine safety and efficacy in mouse models of neuropathic pain. Continued development of this film delivery system may lead to a new, non-opioid therapeutic strategy that could be combined with local anesthesia for up to 4 days after surgery to reduce or potentially eliminate opioids use.

Health care services for patients with both chronic pain and opioid use disorder are fragmented in the United States. To develop effective and feasible interventions for chronic pain and opioid misuse/disorder that can be implemented in both general medical and addiction treatment settings, this research examines two different care-delivery strategies. The first project will compare the effectiveness of a pharmacist-led, collaborative care approach for patients prescribed long-term opioids who have chronic pain and  opioid misuse/disorder compared to a pharmacist program with a cognitive behavior therapy-based pain self-management program. The second project will examine the effectiveness of a multimodal, interdisciplinary chronic pain management program that includes cognitive behavioral therapy, exercise, and stress management. With input from stakeholders and individuals with lived experience, this research has the potential to generate novel, reproducible, and scalable findings that addresses fragmented care delivery for co-occurring chronic pain and opioid misuse/disorder.

The objective of the HBCD PRELUDE (Prenatal Experiences and Longitudinal Development) multi-site consortium is to characterize typical brain development from birth through childhood. All sites in this consortium will measure the influence of key biological and environmental factors on child social, cognitive, and emotional development. Researchers will assess how prenatal exposure to opioids and other substances, as well as other adverse environmental factors, affect brain development and other child health outcomes. The Vanderbilt University site will enroll a diverse sample of mother-infant dyads reflective of the racial, ethnic, and economic composition of the demographics of Tennessee, including rural areas dramatically affected by the opioid crisis.

The parent project’s Housing First initiative can be divided into two interconnected goals: (1) to reduce the likelihood of substance misuse and the development of an opioid use disorder and (2) to provide youth with housing stability and opioid and related risk prevention services that will assist them in exiting homelessness. The proposed supplement project complements the goals of the parent grant project by exploring two additional components that are related to exiting homelessness and reducing substance misuse or the development of opioid use disorder: (1) to further investigate youth’s interactions with social service providers, via qualitative methods, with the goal of cultivating a detail understanding actionable practices as it relates to fostering successful interactions between substance using homeless youth and service providers and (2) to evaluate, via quantitative methods, the extent to which ethnic identity protects youth from the negative effects of discrimination, substance misuse, and the development of a opioid use disorder.

The need to develop non-opioid therapeutics for chronic pain is greater than ever.  One option being explored is inhibiting the activity of calpains – enzymes that have been shown to cause pain in animal models of chronic pain.  Using an artificial intelligence (AI)-driven drug discovery platform, researchers have uncovered and validated four calpain-1 inhibitors using biochemical assays.  This study by 1910 Genetics Inc. hopes to synthesize multiple analogs of its most potent discovered calpain-1 inhibitor and determine its effectiveness against calpain-2 and certain enzymes that break down proteins.  Findings that successfully significantly inhibit calpain-1 in at least one animal model of chronic pain could lead to the first oral, central nervous system penetrating selective calpain-1 inhibitor [non-opioid therapeutic] for chronic pain.

Chronic pain and opioid use disorder often occur together, but there are a striking lack of integrated treatments accessible to people in need, particularly Black and Hispanic individuals living and seeking care in under resourced settings. This research will examine multi-modal, evidence-based practices in diverse health care settings and among diverse populations with both chronic pain and opioid misuse/disorder. The first project will examine the effects of yoga and physical therapy onsite at methadone opioid treatment clinics. The second project will test Acceptance and Commitment Therapy and a care-management smartphone app for individuals in primary-care based buprenorphine treatment. The third project will compare microdosing versus standard doses/timing of buprenorphine for hospitalized patients. All three projects will improve access to care for Black and Hispanic individuals in under resourced settings by bringing integrated treatments to them. The interventions have high potential to be used broadly.