Funded Projects

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.

A major barrier to developing new pain treatments has been the absence of infrastructure to facilitate well-designed and carefully conducted clinical trials to test the efficacy of promising treatments. The UF Health Specialized Clinical Center Network will include UF Health as “hub” and statewide partners serving as spokes as part of the EPPIC Network. The University of Florida (UF) has the capability to reach more than 50% of the population of Florida, the third most populous state of the United States, and the capacity to successfully enroll patients with varying pain conditions into clinical trial protocols through its hub and spoke infrastructure as part of EPPIC-Net.

It is increasingly clear that the microbiome influences psychoneurological symptoms, including pain. This project will support clinical research training focused on examining the relationship between the composition and function of the gut microbiome, including the symbiotic bacteria residing in the gut and their functional gene content, and chronic pain among adults with end-stage kidney disease (ESKD). It provides an opportunity for the trainee to expand his skill set as a pain investigator, through experience in implementing and evaluating pain management interventions in adults with ESKD and chronic pain receiving maintenance hemodialysis. The project aims to determine the acceptability of collecting feces and the feasibility of fecal data collection procedure to determine the best strategies for recruiting research participants from multiple dialysis facilities. These steps will allow the exploration of gene content of the gut microbiota and short-chain fatty acids among people with ESKD on maintenance hemodialysis before and after pain management interventions.

The University of Michigan (UM) will lead a Mechanistic Research Center (MRC) as part of the broader BACPAC initiative that will take patients with chronic low back pain (cLBP) and use a patient-centric, SMART design study to follow these individuals longitudinally as they try several different evidence-based therapies while mechanistic studies are overlaid to draw crucial inferences about what treatments will work in what patient endotypes. Interventional Response Phenotyping describes the need in any precision medicine initiative to phenotype participants based on what therapies they do and do not respond to so that one can later link mechanistically distinct disease endophenotypes with those who preferentially respond to therapies targeting those mechanisms.

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’s HEAL Initiative aims to support collaboration between clinical research experts in academia and industry to accelerate the development of highly efficacious, nonaddictive analgesics for well-defined chronic pain syndromes. The University of Rochester (UR), and its leadership for the UR Hub and Spokes within Early Phase Pain Investigation Clinical Network (EPPIC-Net), will recruit subjects with a broad range of pain conditions, with a focus on leveraging clinical trial infrastructure to support patient recruitment and retention, timely and accurate data entry, and regulatory documentation, as well as recruit additional Spoke sites through a national network of analgesic researchers.

EPPIC-Net will provide a robust and readily accessible infrastructure for the rapid implementation and performance of high-quality comprehensive studies of patients with well-defined pain conditions, and the rapid design and performance of high-quality Phase 2 clinical trials to test promising novel therapeutics for pain. Using the Hospital of the University of Pennsylvania as a hub and five additional centers that are part of the UPenn Health System and the Children’s Hospital of Philadelphia (CHOP) as spokes, studies will be conducted as designed by the expertise of the EPPIC Network, which intends to bring intense focus to relatively small numbers of patients with clinically well-defined pain conditions and high unmet therapeutic needs. The UPenn Specialized Clinical Center (SCC) will test novel, efficient study designs including adaptive and platform designs, validation studies of biomarkers, and biomarker-informed proof of principle or target engagement studies in Phase 2 trials of interventions from academic and industry partners.

The University of Pennsylvania Perelman School of Medicine serves as the Scientific and Data Research Center (SDRC) for the Hemodialysis Opioid Prescription Effort (HOPE) Consortium. Specifically, the SDRC will 1) provide scientific leadership for the HOPE Consortium clinical trial; 2) provide comprehensive operational support to the Clinical Centers for implementing the collaboratively designed trial protocol; 3) develop and lead a Stakeholder Engagement Working Group; 4) integrate and analyze data from the electronic health records of the participating Clinical Centers; 5) establish, promote, and maintain consortium-wide high standards for quality assurance and practices; 6) initiate and oversee contracts with industry partners; 7) prepare reports for the Data and Safety Monitoring Board, and support the preparation of Consortium reports of scientific findings; 8) prepare, document, and transfer Consortium data and biosamples to a Central Repository; and 9) develop approaches for disseminating the trial findings to diverse stakeholders.

Research on optimal long-term opioid therapy (LTOT) tapering strategies has lagged behind clinical needs. Patients with end-stage renal disease (ESRD) receiving hemodialysis (HD) may be especially vulnerable. This study will adapt the Collaborative Opioid Reassessment Program (CORP) and Cooperative Pain Education and Self-Management (COPES) interventions for patients receiving HD and LTOT and test their effectiveness in a pragmatic sequential multiple assignment randomized trial (SMART) design. Initial randomization will be to compare CORP-supported taper with (CORP-B) and without (CORP) buprenorphine rotation on the six-month composite outcome of LTOT dose reduction and pain response. This design will allow determination of which of the eight adaptive treatment strategies leads to the greatest reduction in six-month opioid dose and pain interference.

The IMPOWR (Integrative Management of Chronic Pain and OUD for Whole Recovery) Dissemination, Education, and Coordination Center (IDEA-CC) will develop infrastructure to amplify and create momentum for the findings of the IMPOWR initiative and other linked research networks. This center will i) rapidly deploy a communication framework to link IMPOWR clinical sites with each other and the larger HEAL research frameworks; ii) develop an educational infrastructure addressing stigma and health disparities in patients with co-morbid chronic pain and opioid misuse/disorder; iii) disseminate research findings effectively to targeted audiences; iv) develop a novel composite screening tool for chronic pain and opioid misuse/disorder; and v) harmonize processes for data collection and common data elements of chronic pain and opioid misuse/disorder measures across the IMPOWR research centers, providing a coordinated platform for gathering data from these studies. This center will rapidly disseminate key findings to stakeholders, clinicians, and patients to improve the health and wellbeing of individuals with co-occurring chronic pain and opioid misuse/disorder.

Cancer remains a leading cause of death among Hispanic/Latino populations in the United States. Compared with non-Hispanic Whites, Hispanic/Latino cancer patients are more likely to experience poor quality of life and inadequate cancer-related care, including less effective pain relief and poor patient‒provider communication. Additionally, Hispanic/Latino populations often have inadequate access to pain treatment, due to both social disparities and language barriers. However, most behavioral and psychosocial oncology research continues to focus on non-Hispanic Whites, and empirically validated and effective treatment interventions, particularly psychosocial interventions, are often not available in Spanish. This project will generate a Spanish-language version of the painTRAINER internet-based coping skills training program that is both linguistically and culturally sensitive and will evaluate its feasibility and acceptability in Hispanic/Latino patients with persistent cancer-related pain.