Funded Projects

The objective of the Early Phase Pain Investigation Clinical Network (EPPIC-Net) and EPPIC- Net initiatives is to rapidly and efficiently translate advances in the neurobiology of pain into treatments for people with chronic and acute pain, conditions associated with a significant burden to both patients and society. The Clinical Coordinating Center (CCC) for EPPIC-Net will promote and facilitate, from initial conception through final analysis, clinical trials in adult and pediatric populations with acute or chronic pain by providing efficient methodological, organizational, and logistical support. The EPPIC-Net-CCC will adopt and establish processes aimed at dramatically increasing the efficiency of multicenter clinical trials, improving the overall quality of clinical trials, promoting patient recruitment and retention as well as increasing the number of clinical investigators and research staff well trained and passionate about leading and conducting multicenter clinical trials.

High rates of relapse and overdose deaths pose significant challenges to the treatment of Opioid Use Disorder (OUD). Anti-opioid immunotherapies (i.e., vaccines and monoclonal antibodies) have great potential to reduce long-term opioid use and overdose, with minimal risk of side effects, when used in conjunction with pharmacological treatments and/or behavioral therapies. The ability of an anti-opioid vaccine to induce antibodies that render an opioid less effective, or less rewarding, and protect from accidental overdose could provide an important therapeutic option for patients undergoing treatment for OUD. The goal of this collaborative study is to design, develop, and evaluate vaccines for use in the treatment of opioid use disorder

Pain in the muscles and surrounding connective tissue (myofascial pain) is a significant and poorly understood health concern affecting hundreds of millions of Americans. There is a great need for tools to assess changes to myofascial tissues in individuals with chronic pain as well as to measure the effect of commonly used therapies. This project will use three imaging tools to look at differences between shoulder tissue in people with myofascial pain compared to those without pain. Using a machine learning approach, this research aims to develop a biomarker signature for myofascial pain, which will be evaluated in a randomized controlled clinical trial based on its ability to predict patient responses to myofascial pain treatments.

There is a compelling need to develop a front line, non-opioid-based acute pain management strategy for outpatient oral surgical procedures. LaunchPad Medical has developed Tetranite® (TN), a novel bone regenerative mineral-organic self-setting adhesive biomaterial. TN has been extensively studied in vivo in a canine jaw model and shown to be effective and well-tolerated. In this project, researchers will demonstrate that drug-loaded TN can be a novel route to providing localized and time release pain medication following wisdom tooth extraction by determining the release profile of various pain medications from TN at different concentrations. The ability to release pain therapeutics in a controlled fashion and directly at the site of injury offers improved pain control following oral surgical procedures without exposing the patient to opioids. This novel approach to pain management can be extended to more invasive orthopedic procedures such as joint replacement, spinal fusions or reconstructive trauma surgery. In Phase II the team will conduct an in vivo study to assess efficacy of medicated TN to address post-operative pain following wisdom tooth odontectomy, optimize incorporation and release of medications in TN formulations, develop cGMP manufacturing process for the compounded product, and ultimately conduct clinical trials for bone void filler using medicated TN.

There are currently no effective non-opioid-based pharmacotherapies for treatment of opioid use disorder (OUD). Glial cell line-derived neurotrophic factor (GDNF) is a beneficial protein normally present in low levels in the adult brain, and there is strong evidence that it has clinical potential as a therapy for OUD and relapse reduction. Researchers have developed a non-invasive approach that bypasses the blood-brain barrier to increase levels of GDNF using intranasal administration of gene nanoparticles that make GDNF protein within the brain. This project will test whether this intranasal GDNF gene therapy can suppress drug craving and reduce the tendency to start using a drug again after a period of abstinence in experimental models, thus providing a long-term therapeutic strategy for reducing opioid craving and preventing relapse.

Buprenorphine (BUP) is an FDA-approved medication-assisted therapy (MAT) that improves outcomes and saves lives in patients with opioid use disorder (OUD). It is available in multiple dosage forms and routes of administration, including daily sublingual (SL) and buccal tablets and films, a monthly subcutaneous (SC) injectable, and a 6-month SC implant; however, these forms leave many patients untreated or undertreated. This product, in a partnership with Lyndra Therapeutics, aims to develop a once-weekly oral BUP dosage form for maintenance therapy for OUD, using a new oral dosage formulation developed by Lyndra. A long-acting oral BUP may address important limitations of current MATs by providing improved PK with less euphoria than SL, a patient- and provider-preferred route of administration, and an optimal dosing interval for improved patient adherence with the potential for cost-effective direct observed therapy.

Risk for opioid use disorder (OUD) often begins in adolescence and young adulthood. Engaging and retaining adolescents and young adults (collectively, “youth”) in early, effective treatment is critical for improving the life course trajectory of addiction. For adults with OUD, office-based opioid treatment (OBOT) with a collaborative care approach that includes behavioral therapy optimizes patient engagement and retention in care. Collaborative care OBOT is especially promising for youth, who can receive treatment from a trusted primary care provider in the same familiar setting they receive their usual medical care. To date, however, OBOT has not been formally adapted for treating youth. The central objective of this project is to develop and pilot an enhanced OBOT model for youth that is developmentally appropriate and family centered. The multidisciplinary nature of our team, which includes expertise in advanced biostatistical analysis, qualitative research, intervention development, developmental psychology, and implementation and improvement science, will maximize the chances of filling an important gap in the provision of youth specific evidence-based OUD interventions.

Although there are effective prevention and treatment programs and services to address opioid misuse, opioid use disorder, and overdose, gaps remain between those needing and those receiving prevention and treatment. There is a need to better understand how to make these programs and services most effective at a local level, a problem being addressed by the HEALing Communities Study. This project supports a scientist from a group underrepresented in biomedicine to continue ongoing work to test the impact of an integrated set of evidence-based practices across health care, behavioral health, justice, and other community-based settings.

Methadone maintenance therapy has been shown to facilitate recovery and prevent deaths from opioid use disorder (OUD). This proposal is for development of a once-weekly oral methadone for maintenance therapy for OUD. Lyndra has developed an oral gastric residence dosage form that has been demonstrated to provide at least seven days of continuous delivery. A once-weekly oral methadone product could lower a major barrier to treatment for many patients, reduce the stigma and socioeconomic impact of medication-assisted therapy, and increase the capacity of methadone treatment centers by reducing the number of patient visits. This study will perform pharmaceutical development and pharmacological characterization of a once-weekly oral methadone dosage form, leading to the selection of a clinical candidate for a first-in-human trial and submission of an IND. Clinical trials will then be performed to evaluate the safety and pharmacokinetics of the once-weekly oral methadone dosage form in subjects with OUD.

Although there are effective prevention and treatment programs and services to address opioid misuse, opioid use disorder (OUD), and overdose, gaps remain between those needing and those receiving prevention and treatment, in part because of a need to better understand how to make these programs and services most effective at a local level. The National Institutes of Health (NIH) and the Substance Abuse and Mental Health Services Administration (SAMHSA) launched the HEALing Communities Study to generate evidence about how tools for preventing and treating opioid misuse and OUD are most effective at the local level. This multisite implementation research study will test the impact of an integrated set of evidence-based practices across health care, behavioral health, justice, and other community-based settings. The goal of the study is to reduce opioid-related overdose deaths by 40 percent over three years. Boston Medical Center is partnering with academic institutions in three other states to study the impact of these efforts in 67 highly affected communities. The study will also look at the effectiveness of coordinated systems of care designed to increase the number of individuals receiving medication to treat OUD, increase the distribution of naloxone, and reduce high-risk opioid prescribing.

Despite psychopathology robustly increasing the risk for later substance use disorders (SUD), remarkably few studies have examined the impact of treating psychopathology on reducing rates of opioid use disorder (OUD), nicotine, and SUD. The main aims of this study are to implement a pragmatic set of office-based instrumentation using patient related outcome measures linked to electronic health records (EPIC) for intake and follow-up assessments to evaluate psychopathology, OUD, nicotine use disorder, and other SUDs in young people aged 16-30 years old who are receiving psychopathology treatment as part of routine outpatient clinical care. The study will also examine similar age patients with non-opioid SUD in outpatient SUD treatment settings to examine the impact of treatment in mitigating the development of OUD. Data derived from this study will help inform clinical guidelines and public health policy and provide important secondary outcomes for further work on the prevention of OUD, nicotine use disorder, and other SUDs in relation to early-onset psychopathology.

Sober Grid™ has developed a smartphone-based mobile application currently in use by more than 120,000 individuals worldwide who are in, or seeking, recovery from drug and alcohol addiction. The “Grid,” as it is known, is a mobile-based, social recovery community providing rapid context-specific peer support, efficient help seeking, motivational enhancement exercises, and member ratings of support content—all aimed to prevent relapse. The overarching goal of this phase II project is to extend the current capabilities of the Sober Grid app to achieve a comprehensive social recovery support app featuring intelligent, context-appropriate resource matching and 24/7 rapid-response peer coaching that is effective in reducing disordered substance use and is cost-effective. This projects tests whether providing this functionality to high-risk members will be acceptable, feasible, increase access to and engagement with resources, and have a positive effect in increasing time to relapse and days of consecutive abstinence.