Funded Projects

This study aims to address critical gaps and unmet therapeutic needs of chronic low back pain (CLBP) patients using a next-generation deep brain stimulation (DBS) device with directional steering capability to engage networks known to mediate the affective component of CLBP. Researchers will utilize patient-specific probabilistic tractography to target the subgenual cingulate cortex (SCC) to engage the major fiber pathways mediating the affective component of chronic pain. The objective is to conduct an exploratory first-in-human clinical trial of SCC DBS for treatment of medically refractory CLBP. The research team aims to: (1) assess the preliminary efficacy of DBS of SCC in treatment of medically refractory CLBP; (2) demonstrate the safety and feasibility of SCC DBS for CLBP; and (3) develop diffusion tensor imaging–based blueprints of response to SCC DBS for CLBP.

Hospital inpatient stays due to opioid-related health problems are a reachable moment for increasing access to treatment with medications for opioid use disorder (MOUD). Hospitalized patients with opioid use disorder (OUD) are at particularly high risk for morbidity, mortality, and high medical costs in the U.S. This study will substantially inform the care management of OUD in hospitalized patients. The project includes a comparative effectiveness research trial and an implementation research trial, which will lead to models of broad dissemination for treatment approaches to this largely unaddressed population. They will examine whether (1) in hospitals with addiction medicine consultation services, hospital-initiated extended-release buprenorphine (XR-BUP), compared with other OUD medications, results in increased engagement in treatment with MOUD following hospital discharge and (2) training hospitals without such consultation services on best practices for initiating MOUD using consultation service hubs improves medication uptake in hospitals and increased MOUD treatment engagement following discharge.

The proposed Fast Track SBIR effort will develop and validate the reliable, low-cost KnowPain instrument. KnowPain will objectively and quantitatively assess the functional impact of chronic pain using measures derived from six degrees-of-freedom motion, heart rate, skin surface temperature, and skin conductivity collected via a specially designed, ergonomic wrist-worn biometric sensing instrument. The new assessment instrument will apply advanced psychometric methods to both physiologic and kinematic data to provide precise scores for functional impairment due to chronic pain. The assessment results will be presented to the clinician in an easy-to-understand report and will include longitudinal results, confidence estimates, and normative data to enable comparisons both within and between patients. The system will include provision to interface with electronic medical records. Accurate functional assessment is a crucial component in the effective treatment of chronic pain. The proposed approach will supplement existing methods for assessing patient function by providing novel and highly complementary information for a more complete (and often unobserved) picture of the impact of chronic pain on patient function. KnowPain measures will provide important data on the practical consequences of pain and on treatment efficacy. 

Despite increased efforts to understand the neurodevelopmental sequelae of in utero opioid and other substance exposure on long-term behavioral, cognitive, and societal outcomes, important questions remain, specifically, 1) How is brain growth disrupted by fetal substance and related pre- and post-natal exposures? and 2) How are these disrupted growth patterns causally related to later cognitive and behavioral outcomes? This project seeks to formulate an approach to addressing these key questions and decipher the individual and cumulative effect of these intertwined pre- and post-natal exposures on child neurodevelopment. First, researchers will address the legal, ethical, and mother-child care and support concerns implicit in this study. Next, they will integrate across our areas of neuroimaging expertise to develop, implement, and harmonize a multi-modal MRI and EEG protocol to assess maturing brain structure, function, and connectivity. Finally, researchers will develop and test advanced statistical approaches to model and analyze this multidimensional and longitudinal data.

For individuals with moderate to severe opioid use disorder (OUD), medication-assisted treatments (MATs) such as oral methadone and extended-release naltrexone (XR-NTX) are the gold standard in initiating and maintaining long-term recovery. Still, many patients struggle with persistent sleep disturbance and stress reactivity in the early stages of recovery, which drive relapse behaviors. This proposal constitutes a novel mechanistic approach to understanding the role of the orexin system in sleep disturbance and circadian rhythms of stress in OUD patients who are maintained on MATs and are early in recovery. This study will determine whether the FDA-approved sleep medication suvorexant (SUVO) improves sleep continuity and decreases diurnal measures of stress, and whether improvement of sleep/stress processes translates to improved OUD treatment outcomes. Its findings will fill critical gaps in our understanding of the role of the orexin system in sleep disturbance and circadian rhythms of stress that impact OUD recovery.

The widespread misuse of opioids has underscored the need to develop nonaddicting pain medications. Chronic pain is a major factor contributing to insomnia, and sleep disruption due to chronic pain causes patients to seek relief, exacerbating the drive for prescription opioids. In opioid use disorder, withdrawal from opiates induces insomnia, posing an additional challenge for successful abstinence. This study aims to determine whether treatment of opioid withdrawal-induced insomnia with nociceptin/orphanin FQ receptor (NOPR) agonists will mitigate the drive for opiate use. A major component of the arousal/withdrawal circuitries resides in the locus coeruleus (LC), which expresses MOPRs. The study will determine whether and how the NOPR system engages LC circuits to reduce arousal and insomnia-related phenotypes and assess the hypotheses that 1) the NOPR system is a component of the endogenous sleep/wake regulatory system and 2) NOPR agonists can act as therapeutic interventions to reduce opiate use.

The UCSF Core Center for Patient-centric Mechanistic Phenotyping in Chronic Low Back Pain (UCSF REACH) is an interdisciplinary consortium of basic and clinical scientists dedicated to understanding and clarifying the biopsychosocial mechanisms of chronic low back pain (cLBP). The goal of REACH is to define cLBP phenotypes and pain mechanisms that can lead to effective, personalized treatments for patients across the population. UCSF REACH has six cores that will support a single research project that is focused on the challenge of developing validated and adoptable tools that enable comprehensive yet routine clinical assessment and treatment of cLBP patients. Overall, the object of REACH is to make optimum use of all available resources to catalyze discovery and translation of novel diagnostics and therapeutics that improve outcomes of cLBP patients.

For patients with end-stage renal disease treated with long-term hemodialysis (HD), the safety and efficacy of behavioral interventions alone or augmented by safer drugs remain untested. This study will perform a multicenter parallel group randomized controlled trial to test the efficacy of two interventions to reduce opioid use in HD patients. Seven hundred and twenty HD patients with significant and ongoing opioid use will be randomly assigned to (1) telehealth cognitive behavioral therapy (CBT) alone, (2) telehealth CBT augmented by transdermal buprenorphine, and (3) usual care, with follow-up for up to one year. The primary outcome will be prescribed morphine milligram equivalent (MME) over the preceding four weeks. Three patient-reported outcomes (interference by pain, functional status, and quality of life) will comprise the secondary outcomes.

Many opioid harm reduction services are designed and implemented to serve urban populations in traditional centers of opioid use and leave rural patients underserved. The proposed project seeks to demonstrate improved MAT participation, naloxone distribution, and syringe support services (SSPs) among justice-involved persons with opioid use disorders, and thus improve health and criminal justice outcomes across diverse urban and rural settings in Illinois. Reducing Opioid Mortality in Illinois (ROMI) is a multi-site trial that will be carried out using a hub-and-spoke model, with centralized long-standing social services infrastructure at the Community Outreach Intervention Projects (COIP) hosted at the University of Illinois at Chicago. COIP provides case management/transition of care services to justice-involved opioid users, extending resources and technical assistance to less-populated rural areas hardest hit by the opioid epidemic.

A persistent problem in the dissemination of medications for opioid use disorder (MOUD) is patient dropout, and matching patients to suitable medication early has the potential to minimize dropout. The overall objective of this secondary data analysis study is to develop and disseminate individual level risk prediction models using harmonized data collected from three multi-site clinical trials from the CTN, in order to predict specific clinical outcomes (e.g., dropout, relapse) for patients treated with MOUD, including methadone, buprenorphine or extended-release depot naltrexone. The relative importance of predictors in the best predictive models will be estimated, which may facilitate refinement of common data elements for future OUD studies. The comprehensive, harmonized database of treatment data created in this study can be used for future secondary data analysis studies and will provide a replicable data pipeline to process and validate OUD data in future protocols.

The U.S. is in the midst of an opioid crisis, and efforts to tackle the complex and dynamic nature of this public health challenge must comprehensively consider a multitude of contributing factors. In response, states have implemented a wide range of policies and initiatives. However, the dynamic nature of the crisis and the speed with which different policy approaches are being implemented pose numerous challenges for researchers evaluating the effects of such efforts. These challenges stem in part from limited information regarding policy implementation; insufficient information about policy characteristics that may influence effectiveness; little consideration of how the chosen analytic method may influence findings, given simultaneous or concurrent implementation of multiple policies; and limited training on how to best communicate findings to policymakers. To address these challenges, the proposed Center for Opioid Policy Research (COPR) will serve as a national resource, fostering innovative and high-quality research in the opioid policy arena and developing and disseminating methods, tools and information to the research community, policymakers and the public.

SER-227 is a long-acting polymer pro-drug of buprenorphine that is being developed to treat post- operative pain following major surgeries such as bunionectomy, abdominoplasty, thoracotomy and knee and hip surgery. The ultimate goal is to demonstrate that SER-227 can be manufactured and tested preclinically to show that it is safe for use in a Phase I clinical study. Aims include 1.SER-227 chemistry and process optimization to generate a technical package, 2. SER-227 manufactured under current Good Manufacturing Practices, 3. Evaluated in formal toxicology studies in rodent and non-rodent animals so that justifications can be made to support a ‘first-in-man’ study, and 4. Submission of an Investigational New Drug application (IND) along with a Phase I clinical  protocol in normal volunteers to measure the safety, tolerability and pharmacokinetics of  buprenorphine that is released from SER-227. 

The growing opioid use epidemic in the U.S. has been associated with a significant increase in the prevalence of pregnant opioid-dependent women and neonatal abstinence syndrome, which is associated with adverse health effects for the infant and with costly hospitalizations. Maintenance with sublingual (SL) buprenorphine (BUP) is efficacious for opioid use disorder but has disadvantages that may be heightened in pregnant women, including the potential for poor adherence, treatment dropout, and negative maternal/fetal effects associated with daily BUP peak-trough cycles. Extended release (XR) formulations may address some of these disadvantages. The primary objective of CTN-0080 is to evaluate the impact of treating opioid use disorder in pregnant women (n = 300) with BUP-XR, compared to BUP-SL, on maternal-infant outcomes. Other objectives include testing a conceptual model of the mechanisms by which BUP-XR may improve maternal-infant outcomes, relative to BUP-SL; determining the economic value of BUP-XR, compared with BUP-SL, to treat OUD in pregnant women; and evaluating the impact of BUP-XR, relative to BUP-SL, on neurodevelopment when the infant/child is approximately 12 and 24 months of age. Ultimately, this study will help in increasing access to treatment as well as provide quality care for pregnant/postpartum women.