Funded Projects

Chemotherapy-induced peripheral neuropathy (CIPN) is detected in 64% of cancer patients during all phases of cancer. CIPN can result in chemotherapy dose reduction or discontinuation, and can also have long-term effects on the quality of life. Taxanes (like Paclitaxel) may cause structural damage to peripheral nerves, resulting in aberrant somatosensory processing in the peripheral and/or central nervous system. Dorsal root ganglia (DRG) sensory neurons as well as neuronal cells in the spinal cord are key sites in which chemotherapy induced neurotoxicity occurs. T-type Ca2+ channels are critical determinants of increased neuronal excitability and neurotransmission accompanying persistent neuropathic pain. Though Cav3.2 has been targeted clinically with small molecule antagonists, no drugs targeting these channels have advanced to phase II human clinical trials. This proposal aims to explore multicomponent reaction products, for the rapid identification of potent and selective T-type Ca2+ channel antagonists. The work proposed here is the first step in developing non-opioid pain treatments for CIPN. The team anticipates success against paclitaxel-induced chronic pain will translate into other chronic pain types as well, but CIPN provides focus for early stage proof-of-concept.

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. This study will take place at Oklahoma State University Center for Health Sciences and recruit diverse people from an urban area, including American Indian populations.

There is evidence that combining mindfulness-based interventions and peer recovery support services with medication-assisted therapy (MAT) to treat opioid use disorders (OUD) reduces substance use, cravings, symptoms of depression and anxiety, and relapse rates, and improves treatment retention, and relationships with treatment providers and social supports. The goal of the present study is to determine the effectiveness of a mindfulness-based intervention that also utilizes peer mentors in addition to professional substance abuse therapists (the Minds and Mentors program [MiMP]) in improving adherence to MAT for OUD and reducing relapse rates in a sample of individuals with OUD who are also on MAT versus a 12-step facilitation (TSF) program. The study hypothesizes that participants in MiMP will demonstrate better adherence; reduced relapse and cravings (primary outcomes measures); reduced depression, anxiety, and stress; improved social support (secondary outcomes measures); and reduced cortisol levels and reactivity to drug cues (exploratory outcome measures).

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 Pennsylvania State University study site is in a region hard hit by opioid and methamphetamine use disorders and will recruit mother-infant pairs from largely rural communities.

With the entwined crises of opioid use and chronic pain, there is a need for alternative, safe therapies to manage opioid use disorder, opioid withdrawal symptoms, chronic pain, and/or associated anxiety and depression. A proof-of-concept preclinical study has already been conducted of a cannabinoid-opioid combination that demonstrated opioid-sparing and synergistic analgesic effects, with the combination providing greater analgesia in a rodent model of chronic pain than a standard dose of the opioid alone. This proposal aims to develop a fixed-dose combination (FDC) of the cannabinoid-opioid that may have improved analgesia with lower opioid doses and thereby lower the risk of dependence, withdrawal, diversion, abuse, and overdose. Preclinical pharmacokinetic and ?in vivo ?safety studies will help determine if co-administration alters the pharmacokinetics and/or respiratory depression related to either compound in rodents.

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.

People with opioid use disorders (OUD) have high rates of co-occurring alcohol, stimulant and other drug disorders, as well as mental disorders. Traditionally, treatment for OUD has been ?siloed? even though these high rates of co-occurring conditions emphasize the need for comprehensive treatment to address holistic needs. As the opioid crisis continues, attention to the whole person and access to comprehensive mental health and substance use treatment as well as primary care is needed. This study aims to better understand co-occurring mental health disorders, alcohol use disorders, and/or other substance use disorders among people with OUD, in the context of innovative integrated care networks for people with OUD. This study examines how innovative OUD treatment models work for individuals with co-occurring mental health and substance use by 1) assessing mental health treatment quality measures and outcomes; 2) testing how these innovative treatment models compare to other OUD treatment for people who have OUD and other substance use disorders; and 3) considering the ways people with OUD access co-occurring disorder care. The findings from this study will provide needed information to improve mental health, alcohol, and other substance use treatment for individuals with OUD, whether or not they are in OUD treatment and may provide information to help move the system from siloed efforts to truly integrated care

Clinician bias causes inequities in healthcare, and interventions are needed to mitigate and eradicate this bias. This project aims to develop and test the impact of two interventions on overcoming clinician implicit bias in the management of pain for children from ethnic minorities treated in the emergency department. The study will include pediatric patients from under-represented minority groups with pain from long-bone fractures or acute appendicitis who are cared for by racially and ethnically diverse caregivers. Researchers will use stakeholder-informed approaches to establish quality of care metrics and then use clinician audit and feedback as well as data from electronic health records to quantify evidence of bias.      

This project aims to develop a novel abuse deterrent formulation (ADF) that will be uniquely designed to prevent abuse of the prescription pill. The study will focus on the development of the ADF with design aspects specifically focused on abuse through insufflation, smoking, injection, and taking multiple pills. The study will also validate the design by putting the pill through a rigorous test following the procedures outlined by the FDA Abuse-Deterrent-Opioids-Evaluation and Labeling guidelines. The study could result in the development of a novel ADF that will be resistant to a wide range of tampering, resulting in a safer formulation and pill design.

Buprenorphine is an effective treatment for opioid use disorder, but its use is limited due to the need for frequent dosing. This project will optimize the molecular features of an injectable, biodegradable, long-acting (3-month) buprenorphine implant that would not require surgical removal. The research aims to advance toward testing in human research participants.

In collaboration with Eolas Therapeutics and the NIH Blueprint Neurotherapeutics Network, AstraZeneca has developed a novel compound for treatment of opioid use disorder, AZD4041, which targets orexin 1 (OX1) receptors in the brain. In animal studies, AZD4041 reduced the motivation to consume opioids or nicotine, reduced relapse-like drug-seeking behaviors, and showed a favorable safety profile. The compound also has proven to be safe in an initial Phase 1 clinical trial in healthy human volunteers. This project will further evaluate the safety (e.g., respiratory depression profile) of AZD4041 in human volunteers, using multiple and increasing doses. Upon successful completion of these studies, the compound will be tested in a proof-of-concept efficacy study in patients with opioid use disorder. If this is successful, the compound will advance to larger Phase 2 and Phase 3 pivotal clinical trial to tests its effectiveness in the treatment of opioid use disorder.

Pain Coping Skills Training (PCST) uses a cognitive behavioral therapy (CBT) approach to teach patients cognitive and behavioral coping skills shown to reduce pain and pain interference (e.g., relaxation, distraction, cognitive restructuring, activity pacing). Randomized controlled trials show that PCST and similar CBT-based interventions, when delivered in a traditional in-person format, can improve pain and functioning in people with cancer and other conditions. Yet these interventions are underused in clinical care due to barriers such as high resource costs, a shortage of therapists trained to deliver them, and travel requirements for patients. This trial aims to deliver evidence-based behavioral pain interventions such as PCST with methods capable of overcoming barriers currently limiting patient access. This will be investigated using a two-arm trial comparing pain relief with the following interventions: painTRAINER in clinic with eight web-based follow-up sessions; enhanced usual care.