Funded Projects

This proposal would address barriers to the NP’s ability to prescribe buprenorphine by incorporating waiver education into NP final semester curriculum. The initial eight hours of training would be provided to students in a face-to-face classroom setting or via live video streaming. The remaining 16 hours would be completed by the NP students through online modules offered by the AANP. Trained NP students would be eligible for one year of peer-to-peer mentorship and inclusion in the MUSC Project ECHO tele-mentoring for new providers. Outcomes to be tracked would be the number of NPs trained who obtain their waiver and the number of individuals treated with MOUD by the NPs trained. Secondary data collected would offer insight into wavier obtainment process and determine need for mentorship for newly waivered providers.

TWIK-related spinal cord K+ (TRESK) channel is abundantly expressed in all primary afferent neurons (PANs) in trigeminal ganglion (TG) and dorsal root ganglion (DRG), mediating background K+ currents and controlling the excitability of PANs. TRESK mutations cause migraine headache but not body pain in humans, suggesting that TG neurons are more vulnerable to TRESK dysfunctions. TRESK knock out (KO) mice exhibit more robust behavioral responses than wild-type controls in mouse models of trigeminal pain, especially headache. We will investigate the mechanisms through which TRESK dysfunction differentially affects TG and DRG neurons. Based on our preliminary finding that changes of endogenous TRESK activity correlate with changes of the excitability of TG neurons during estrous cycles in female mice, we will examine whether estrogen increases migraine susceptibility in women through inhibition of TRESK activity in TG neurons. We will test the hypothesis that frequent migraine attacks reduce TG TRESK currents.

Prescriptions for narcotic pain relief after surgery result in unintended prolonged opioid use for hundreds of thousands of Americans. Nonpharmacological pain care is effective and recommended by guidelines for perioperative pain while offering a more favorable risk-benefit ratio. However, nonpharmacological pain care is rarely used as first or second-line therapy after surgery. Patient and clinician decision support interventions are effective in encouraging patient-centered and guideline-concordant care, but these strategies have not been tested pragmatically as a bundle in everyday postoperative pain care. The NOHARM trial will first confirm the feasibility of patient-facing and clinician-facing decision support components of an EHR-embedded evidence-based bundle. The investigators will test the bundle in a stepped-wedge cluster randomized trial. They will test a sustainable system strategy that could change the paradigm of perioperative pain management toward nonpharmacological options in a manner that preserves patient function, honors patient values, and maintains availability of opioids as a last resort.

Fibromyalgia (FM) is a chronic pain condition characterized by widespread musculoskeletal pain, tenderness, and stiffness associated with fatigue and sleep disturbance. The investigators have recently completed a trial that demonstrated efficacy of active transcutaneous electrical nerve stimulation (TENS) compared with placebo TENS or no treatment in women with FM. While physical therapists are trained in using TENS, it is underused in clinical practice. This application proposes a pragmatic clinical trial of TENS for patients with FM to determine if the addition of TENS to physical therapy (PT) reduces pain, increases PT adherence, and helps achieve functional goals with less drug use. This study will address the critical need for strategies to implement effective nonpharmacologic treatments for FM. Successful completion of this trial will provide generalizable effectiveness data for referring providers, physical therapists, and insurers and will inform future pragmatic trials of nonpharmacologic treatments conducted in PT practices.

Less than half of youth in the juvenile justice system who meet the criteria for substance use disorders (SUD) have ever received treatment, and less than one third of those received treatment while under community or correctional supervision. SUDs during adolescence can lead to significantly longer periods of substance use, more severe offending, and penetration in the justice system. The Translational Research on Interventions for Adolescents in the Legal System (TRIALS) cooperative is intended to develop and test implementation strategies and associated measures to improve the continuum of substance abuse and HIV prevention and treatment services delivered to youth under juvenile justice supervision.

Quality implementation of evidence-based programs (EBPs) in community settings for youth is critical for reducing the burden of alcohol, tobacco and other drug (ATOD) use and its consequences. EBPs delivered in schools are an efficient way to reach large populations of young people, including those underserved by other settings, and reduce and prevent ATOD use. Yet youth rarely receive EBPs as intended in community settings, including schools. This training and research plan will prepare the investigator to become an independent scholar in the implementation of theories and frameworks to better understand factors related to program delivery—approaches to enhancing ATOD programs for youth in community settings. More specifically, the training will allow him to expand the application of Consolidated Framework for Implementation Research (CFIR) to inform approaches to enhancing effective EBP delivery. The proposed training and research plan extends current implementation research to focus applying implementation theories, frameworks and strategies in other community settings (schools) and on economic evaluation of implementation strategies. The results are expected to improve current efforts to deliver EBPs in diverse community settings and aid in applying evidence-based implementation strategies in the school context to ultimately reduce and prevent ATOD use among youth.

This study will evaluate novel strategies to reduce opioid use and pain in patients with end-stage renal disease receiving chronic hemodialysis (HD). Specifically, the study will examine the effect of nonpharmacologic (Acceptance and Commitment Therapy [ACT] and acupuncture) and pharmacologic (buprenorphine) interventions in HD patients who are receiving chronic opioid medications due to chronic pain and/or high pain interference. The study will enroll 720 HD patients across U.S. Hemodialysis Opioid Prescription Effort Consortium Clinical Centers to (1) determine the effectiveness of ACT and acupuncture compared with the control condition in reducing opioid dose and improving pain among HD patients; (2) identify the best adaptive intervention sequence for improved outcomes; (3) explore age, sex, and comorbidities as potential moderators of the response to the intervention; and (4) describe facilitators and barriers to the implementation of the intervention using in-depth, semi-structured individual interviews with intervention participants and providers.

There is a critical need to expand research infrastructure to develop, test, and implement new clinical interventions and evidence-based opioid use disorder (OUD) treatment into diverse clinical settings. The University of Utah’s Greater Intermountain Node (GIN) will expand the existing NIDA Clinical Trial Network’s (CTN) infrastructure by developing and testing innovative OUD interventions, expanding the settings for CTN research, and bringing new research acumen to the CTN. GIN brings expertise in three spheres of OUD research: (1) non-addiction health care settings, (2) large health systems of care, and (3) implementation science. GIN’s specific aims include (1) enhance CTN’s ability to conduct research in primary care and non-addiction care settings; (2) enhance CTN’s ability to conduct research within integrated systems of care with “big data” resources; and (3) enhance CTN’s implementation of science research to integrate and disseminate evidence-based addiction care into diverse non-addiction and health system targets.

EicOsis is developing a first-in-class analgesic with efficacy against neuropathic pain that will reduce or replace the need for opioids and thus potentially prevent opioid use disorder (OUD). The target of the small molecule inhibitor EC5026 is the soluble epoxide hydrolase, a master regulatory enzyme that modulates the activity of endogenous bioactive lipids. The study will reach the next steps in clinical human clinical trials with EC5026 through additional preclinical studies to expand the efficacy into models of chronic pain conditions. Additionally, detailed pharmacokinetic, metabolism, and distribution studies are proposed that will provide the required information to optimize drug formulation and for advanced clinical trials examining efficacy in humans. EicOsis is meeting current development goals, and EC5026 is well positioned to meet the urgent need of reducing opioid use.

The overarching goal of the Greater Southern California Node (GSCN) of the National Drug Abuse Treatment Clinical Trials Network (CTN) is to expand access to and improve outcomes of treatments for substance use disorders (SUDs)—with a special emphasis on opioid use disorder (OUD). The specific aims of GSCN include the development of new research protocols, support of multi-site CTN projects, and dissemination of research findings. The GSCN research agenda includes four priority areas: (1) developing and testing effective interventions for OUD and related comorbidities, (2) applying implementation science to deliver and expand OUD treatment, (3) leveraging electronic health record systems and data science generation of innovative approaches to improve treatment for OUD, and (4) expanding OUD treatment access and utilization through mHealth and other technologies. The GSCN research agenda reflects its capacity to collaboratively expand CTN efforts to develop and implement innovative approaches to improve treatment for OUD.

The Pain Reduction and Opioid Medication Safety in ESRD (PROMISE) study aims to improve the safety of opioid use and pain management in end-stage renal disease (ESRD) patients on hemodialysis (HD) using a Type I effectiveness-implementation hybrid design. A multisite randomized controlled trial of HD patients from the Hemodialysis Opioid Prescription Effort (HOPE) Consortium will examine the effectiveness of two separate nine-month evidence-based interventions: 1) Opioid Tapering Management (OTM) and 2) Behavioral Pain Management (BPM). We will examine the effectiveness of OTM (versus no OTM, Aim 1) and BPM (versus no BPM) over nine months for reducing opioid use (primary outcome) and improving pain severity (secondary outcome) in HD patients on chronic opioids. The implementation goal will take advantage of the diverse patient, provider, and organizational settings in the HOPE Consortium to evaluate process outcomes.

The Pain Management Collaboratory Coordinating Center (PMC3) will 1) provide national leadership and technical expertise in all aspects of research supporting the design and execution of high-impact demonstration projects that conduct cost-effective, large-scale, pragmatic clinical trials on non- pharmacological approaches for pain management and other comorbid conditions in veteran or military health care systems and 2) make data, tools, best practices, and resources from these and other projects available to facilitate research partnerships in VA and DoD health systems. The aims are to: 1) develop, adapt, and adopt technical policy guidelines and best practices for the effective design and conduct of pragmatic trials; 2) work collaboratively with and provide operational, technical, design, and other support to demonstration project teams to develop, initiate, and implement a research protocol; and 3) disseminate NIH–DoD–VA Pain Management Collaboratory–endorsed policies and best practices and lessons learned within military and veteran health care systems.

The adverse effects of morphine and other mu-opioid receptor (MOR) agonists are linked to the ?-arrestin pathway, while analgesia is tied to the G-protein pathway. Pathway specific or “biased” drug development can target G-protein specific agonists that avoid the negative consequences of ?-arrestin signaling activation and produce analgesia. Highly “biased” MOR agonists have promise as effective analgesics but devoid of opioid-induced adverse effects. Preclinical studies compared two compounds, MEB-1166 and MEB-1170, against Oliceridine and morphine. Both compounds displayed no respiratory depression, even at high doses, while morphine and Oliceridine significantly reduced respiratory function. In contrast to morphine, neither MEB-1166 nor MEB-1170 produced conditioned place preference, suggesting an absence of abuse liability. This study will characterize the pharmaceutical and pharmacological profiles and perform liability studies for these compounds.