Clinical Optimization of Ultrasonic Drug Delivery Technologies for US Veteran Populations that Experience Health Disparities with Arthritis and Chronic Pain

Zetroz Systems, Llc, Trumbull CT

Investigators

Abstract

Narcotic use in pain management of United States veterans and citizens has played a major role in the ongoing opioid crisis. According to the NIH, veterans are susceptible to opioid addiction and are 40% more likely to suffer from severe chronic joint pain then non-veterans. Over the next decade, the percentage of Black, Asian American and Hispanic veterans will increase from 23% to 34% and is expected to rise. This shift of racial and ethnic minorities directly correlates to the growing demographics of Black, Asian American and Hispanic active-duty soldiers that make up over 40% of our nation’s military forces. The federal government considers the 18.2 million veteran and 42 million non-veteran minority Americans to be "potentially vulnerable patient populations” with health disparities particularly related to joint diseases care. Osteoarthritis (OA) is one of the most common of these joint diseases affecting the entire US population, and of considerably higher 19-fold incidence and prevalence in the service-disabled veteran population. Although the disease itself does not appear to occur more frequently in Black, Asian American, and Hispanics, its effects and progression are more severe. This is especially true among Black, Asian American and Hispanics with arthritis, 36.7% of Black patients and 35.5% of Hispanic patients reported severe joint pain compared to only 23.0% of non-Hispanic Whites. The economic healthcare cost of veterans with OA is estimated to approach or exceed $60 billion annually due to longer life expectancies. Arthritis is also a significant economic and health cost in the United States at large which is estimated to exceed $394 billion in healthcare expenditure by 2030. In our SBIR HEAL Phase I, we developed a wireless long-duration low-intensity ultrasound NSAID-enhanced (2.5% diclofenac) sonophoresis system for use by the US veteran population that experience health disparities withOA. We first demonstrated that the sonophoresis technology could increase tissue penetration of NSAIDs by 3.8x compared to standard of care (p<0.01). Secondly, the miniature device was evaluated in a 25-subject human-factors study, 54-subject diathermy study and a 52-subject OA clinical study on patients with radiographically confirmed mild to moderate knee OA. In 8-weeks of daily 4-hour use, symptomatic pain was significantly reduced by 3.43 point (55%) NRS (n=34, p<0.0001) versus 1.00 point (22%) NRS (n=18, p=0.0847) for subjects treated with topical diclofenac pain cream. Over 98% of the study population found the device easy to use and would continue treatment for their knee OA symptoms. For this Phase II HEAL renewal application (1) First ZetrOZ Systems will refine the design and optimize the wireless sonophoresis technology for shelf-life stability and device functionality/usability by the veteran and aging population. A series of regulatory testing standards including sensitization, cytotoxicity, packaging/formulation stability, biocompatibility, microbial growth, shelf-life and home-use will be completed on the wireless sonophoresis system. Additionally, a porcine animal model with histopathology and pharmacokinetics will be completed to verify the safety profile of the technology. (2) ZetrOZ Systems will complete a 24-week, 3-arm, multi-site, placebo-controlled, randomized, efficacy study to expand upon our Phase I study by examining the health benefits and commerciality of the sonophoresis technology in 300 patients enrolled at three ethnically diverse locations. The primary outcome of the study will be pain score, evaluated daily using the numerical rating scale (NRS). Baseline NRS score will include the first two weeks of the study without intervention. The intervention phase will separate three demographically equivalent groups of 100, assigned to use either the medicated/unmedicated sonophoresis technology or standard 2.5% diclofenac topical cream daily self-applied for 24 weeks. The proposed combination therapy has the potential to deliver a safe, effective, and conservative treatment approach for OA across the Black, Asian American and Hispanic veteran and aging populations.