Funded Projects

The ACT NOW Outcomes of Babies with Opioid Exposure (OBOE) Study – also called the ACT NOW Longitudinal Study – is a longitudinal cohort study to prospectively examine longitudinal outcomes from birth to 2 years of age among infants who were exposed to opioids in utero as compared to matched controls. The objectives of this study are to i) determine the impact of pre-birth opioid exposure on brain structure and connectivity over the first 2 years of life, ii) define medical, developmental, and behavioral outcomes over the first 2 years of life in infants exposed to opioids, and iii) Explore whether and how the home environment, maternal mental health, and parenting affect brain connectivity and neurodevelopment trajectories over the first 2 years of life. This research will use an innovative approach to engage a more diverse study population and thereby improve the generalizability of the research findings.

Chronic overlapping pain conditions represent up to half of all chronic pain cases and can be more debilitating than other forms of chronic pain. These conditions include but are not limited to the following: temporomandibular disorders, fibromyalgia, irritable bowel syndrome, vulvodynia, interstitial cystitis/painful bladder syndrome, painful endometriosis, chronic tension type headache, migraine headache, chronic low back pain, and chronic fatigue syndrome. Common neurobiological mechanisms have been suspected to account for the overlap between these conditions, but until recently it has been difficult to efficiently classify each condition within individual patients. A digital classification tool for clinicians has been developed for this purpose, but access to the tool remains limited. Here we propose converting this chronic overlapping pain conditions classification tool into a common web-based application format.

The NIH Back Pain Consortium (BACPAC) Research Program brings together leading centers with expertise in studying and treating chronic low back pain to advance understanding of the mechanisms that underlie the condition and to identify novel treatment strategies. BACPAC is undertaking a multisite precision medicine clinical trial taking into account patient-specific information to understand which patients with chronic low back pain respond best to various nonopioid, evidence-based treatments. The trial seeks to enroll a racially, ethnically, and socioeconomically diverse patient population to ensure that the results are applicable to all Americans with chronic low back pain. This project aims to develop comprehensive recruitment and retention plans for study sites that can recruit from historically underrepresented populations in clinical research (e.g., Black and Hispanic populations) and to provide dedicated financial resources to engage patients from these populations using tailored, culturally appropriate strategies.

Understanding municipal policies that influence implementation of effective evidence-based practices (EBPs) as well as effective strategies for working with municipal groups may inform local efforts to translate EBPs. Just as important, engaging with local stakeholders may help to facilitate the long-term sustainability of EBPs. This can only occur if diverse local actors in municipal governance are thinking about health and behavioral health in the context of municipal planning and policy. Building from research related opioid use disorder and the risk environment, built environment, and zoning, this research will work to support coalition-based approach currently implemented by the HEALing Communities Study. The research aims to develop an understanding of local policies that may affect implementation of community action plans in the HEALing Communities Study Massachusetts communities.

Pain caused by the degeneration of discs between vertebrae in the spine makes up a significant proportion of all chronic low back pain conditions. Although opioids are prescribed as treatments for this chronic condition, they often do not provide effective pain management, and currently there are no treatments that target the underlying disc disease. Notochordal cells mature into the cells that make up discs between vertebrae. Preliminary studies have shown that notochordal cells can be made from induced pluripotent stem cells, offering a potential replacement for diseased cells between discs. This study aims to develop a novel treatment for painful disc degeneration using a microgel/microtissue embedded with human notochordal cells made in the lab from induced pluripotent stem cells.

Spinal cord stimulation (SCS) has been shown to provide effective relief for most people with chronic pain and eliminated the need for opioid therapy in more than half of those treated. However, traditional SCS approaches have encountered problems when glial cells coat the stimulation electrodes that distance the device from targeted neurons. This project will develop a novel hybrid Closed Loop Omnidirectional Neuromodulation with Electromagnetic fields (CLONE) system that is combined with magnetic-based stimulation to overcome glial coating of SCS electrodes, better target neurons in dorsal spine tissue, which may lead to better treatment of chronic neuropathic neck and low back pain.

G protein-coupled receptors (GPCRs) are the largest family of transmembrane signaling proteins and play important roles in inflammation and pain. GPCR signaling is fast and temporary, making it hard to measure in clinical studies of potential drugs to interfere with the signaling. This research is using selectively designed nanoparticles to stimulate or block GPCRs toward identifying new treatments for oral cancer pain. This award will use a new nanoformulation approach to understand how nanoparticles affect nerve function by i) testing the effects of continuous release of a GPCR inhibitor in an oral cancer microenvironment and ii) investigating the influence of various physicochemical characteristics of nanoparticles on nerve function in an oral cancer microenvironment.

Efforts to identify non-opioid analgesics for treatment of chronic pain have identified a protein, carbonic anhydrase-8 (CA8), in pain-sensing nerve cells in the spinal cord (dorsal root ganglion cells) whose expression regulates analgesic responses. Gene therapy delivering CA8 to dorsal root ganglion cells through clinically relevant routes of administration functions as a “local anesthetic” that induces long-lasting pain relief in animal models of chronic pain. This project will further develop CA8 gene therapy with the goal of treating chronic knee osteoarthritis pain. It will assess several gene therapy constructs to determine the doses needed, safety, efficacy, and specificity to nerve cells for each construct. It will then select the safest and most effective construct that can be administered via the least invasive route for further development. The project will include all steps necessary to identify one candidate gene therapy construct that will be suitable to begin clinical trials in patients with chronic knee osteoarthritis pain.

Chemokines (hormones of the immune system that mediate innate immune inflammation) enhance pain, reduce opioid analgesia, and promote drug-seeking behavior and addiction, giving them a central role at the crossroads of chronic pain and the opioid crisis. Blocking chemokines (rather than opioid receptors) provides an exciting treatment opportunity for both pain and opioid use disorder. This research continues previous work studying the efficacy of RAP-103, a small, orally stable chemokine receptor blocker. The previous research has shown that RAP-103 is safety and effective in preclinical models that mimic human drug-taking. This research will now optimize the dose required to achieve decreased motivation to maintain opioid use, establish manufacturing scale-up feasibility, provide RAP-103 for safety testing in animals, and conduct stability testing of RAP-103 toward the goal of submitting an Investigational New Drug application to the FDA.

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.

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 research dataset to the scientific community. 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 Cedars-Sinai Medical Center study site is in Los Angeles where marijuana is legal and methamphetamine use is prevalent, enabling researchers to recruit participants from high-risk 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.

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. 

This site will serve as the Data Coordinating Center for the clinical trial to provide high-quality and impartial biostatistical expertise for all the study sites.