R44MD015912

Clinical Optimization of Ultrasonic Drug Delivery Technologies for Underserved Minority US Veterans in Chronic Pain - Project Summary:

Narcotic use in pain management of underserved minority populations and minority United States veterans has played a major role in the ongoing opioid crisis. According to the NIH, veterans are more susceptible to opioid addiction and are 40% more likely to suffer from severe chronic joint pain than non-veterans.

Over the next decade, the percentage of minority 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 minority 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 minorities, its effects and progression are more severe. This is especially true among minorities 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 burden 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 burden in the United States at large, which is estimated to exceed $394 billion in healthcare costs 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 underserved OA population. 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 points (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 minority, veteran, and aging populations.

Zetroz Systems

TO SUPPORT BASIC, CLINICAL, SOCIAL, AND BEHAVIORAL RESEARCH, PROMOTE RESEARCH INFRASTRUCTURE AND TRAINING, FOSTER EMERGING PROGRAMS, DISSEMINATE INFORMATION, AND REACH OUT TO MINORITY AND OTHER HEALTH DISPARITY COMMUNITIES. THE NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES (NIMHD) HAS ESTABLISHED PROGRAMS TO PURSUE THESE GOALS: (1) THE CENTERS OF EXCELLENCE PROGRAM PROMOTES RESEARCH TO IMPROVE MINORITY HEALTH AND/OR REDUCE AND ELIMINATE HEALTH DISPARITIES, BUILDS RESEARCH CAPACITY FOR MINORITY HEALTH AND HEALTH DISPARITIES RESEARCH IN ACADEMIC INSTITUTIONS, ENCOURAGES PARTICIPATION OF HEALTH DISPARITY GROUPS AND COMMUNITIES IN BIOMEDICAL AND BEHAVIORAL RESEARCH AND PREVENTION AND INTERVENTION ACTIVITIES, AND BRINGS TOGETHER INVESTIGATORS FROM RELEVANT DISCIPLINES IN A MANNER THAT WILL ENHANCE AND EXTEND THE EFFECTIVENESS OF THEIR RESEARCH, (2) NIMHD RESEARCH ENDOWMENT PROGRAM BUILDS RESEARCH CAPACITY AND INFRASTRUCTURE AT ELIGIBLE NIMHD CENTERS OF EXCELLENCE OR ELIGIBLE SECTION 736 HEALTH PROFESSIONS SCHOOLS (42 U.S.C. 293) TO FACILITATE MINORITY HEALTH AND OTHER HEALTH DISPARITIES RESEARCH TO CLOSE THE DISPARITY GAP IN THE BURDEN OF ILLNESS AND DEATH EXPERIENCED BY RACIAL AND ETHNIC MINORITY AMERICANS AND OTHER HEALTH DISPARITY POPULATIONS, PROMOTES A DIVERSE AND STRONG SCIENTIFIC, TECHNOLOGICAL AND ENGINEERING WORKFORCE, AND EMPHASIZES THE RECRUITMENT AND RETENTION OF UNDERREPRESENTED MINORITIES AND OTHER SOCIO-ECONOMICALLY DISADVANTAGED POPULATIONS IN THE FIELDS OF BIOMEDICAL AND BEHAVIORAL RESEARCH AND OTHER AREAS OF THE SCIENTIFIC WORKFORCE, (3) THE CENTERS OF EXCELLENCE ON ENVIRONMENTAL HEALTH DISPARITIES RESEARCH TO STIMULATE BASIC AND APPLIED RESEARCH ON ENVIRONMENTAL HEALTH DISPARITIES, (4) MINORITY HEALTH AND HEALTH DISPARITIES INTERNATIONAL RESEARCH TRAINING PROGRAM (MHIRT) AWARDS ENABLE U.S. INSTITUTIONS TO TAILOR SHORT-TERM BASIC SCIENCE, BIOMEDICAL AND BEHAVIORAL MENTORED STUDENT INTERNATIONAL RESEARCH TRAINING OPPORTUNITIES TO ADDRESS GLOBAL ISSUES RELATED TO UNDERSTANDING, REDUCING, AND ELIMINATING HEALTH DISPARITIES, (5) SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM INCREASES PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, ENCOURAGES SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND FOSTERS AND ENCOURAGES PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION, (6) SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATES AND FOSTERS SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, FOSTERS TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, INCREASES PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND FOSTERS AND ENCOURAGES PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION, (7) HEALTH DISPARITIES RESEARCH PROJECT GRANTS (RPG) SUPPORT INNOVATIVE PROJECTS TO ENHANCE OUR UNDERSTANDING OF BIOLOGICAL MECHANISMS, SOCIAL, BEHAVIORAL, AND HEALTH SERVICES THAT CAN DIRECTLY AND DEMONSTRABLY CONTRIBUTE TO THE IMPROVEMENT IN MINORITY HEALTH AND THE ELIMINATION OF HEALTH DISPARITIES WHICH INCLUDES THE (8) RESEARCH CENTERS IN MINORITY INSTITUTIONS (RCMI) BUILD CAPACITY FOR BASIC BIOMEDICAL AND/OR BEHAVIORAL RESEARCH, CLINICAL AND TRANSLATIONAL RESEARCH (RCTR) AND A NETWORK (RCTN) BY FOCUSING ON INSTITUTIONAL RESOURCE DEVELOPMENT, SUCH AS SUPPORTING CORE RESEARCH FACILITIES AND STAFF, PURCHASING ADVANCED INSTRUMENTATION, AND LABORATORY RENOVATIONS/ALTERATIONS (9) CLINICAL RESEARCH EDUCATION AND CAREER DEVELOPMENT (CRECD) AWARDS PROVIDE DIDACTIC TRAINING AND MENTORED CLINICAL RESEARCH EXPERIENCES TO DEVELOP INDEPENDENT RESEARCHERS WHO CAN LEAD CLINICAL RESEARCH STUDIES, ESPECIALLY THOSE ADDRESSING HEALTH DISPARITIES, (10) PATHWAY TO INDEPENDENCE AWARDS (K99/R00) TO INCREASE AND MAINTAIN A STRONG COHORT OF NEW AND TALENTED, NIH-SUPPORTED, INDEPENDENT INVESTIGATORS. (11) NIH RESEARCH CONFERENCE GRANT AND NIH RESEARCH CONFERENCE COOPERATIVE AGREEMENT PROGRAMS SUPPORT HIGH-QUALITY CONFERENCES THAT ARE RELEVANT TO THE MINORITY HEALTH AND HEALTH DISPARITIES, (12) TRANSDISCIPLINARY COLLABORATIVE CENTERS FOR HEALTH DISPARITIES RESEARCH COMPRISE REGIONAL COALITIONS OF ACADEMIC INSTITUTIONS, COMMUNITY ORGANIZATIONS, SERVICE PROVIDERS AND SYSTEMS, GOVERNMENT AGENCIES AND OTHER STAKEHOLDERS CONDUCTING COORDINATED RESEARCH, IMPLEMENTATION AND DISSEMINATION ACTIVITIES THAT TRANSCEND CUSTOMARY APPROACHES AND SILO ORGANIZATIONAL STRUCTURES TO ADDRESS CRITICAL QUESTIONS AT MULTIPLE LEVELS IN INNOVATIVE WAYS FOCUSED ON PRIORITY RESEARCH AREAS IN MINORITY HEALTH AND HEALTH DISPARITIES, (13) RUTH L. KIRSCHSTEIN NRSA INDIVIDUAL PREDOCTORAL FELLOWSHIP

93.279 - Drug Abuse and Addiction Research Programs

National Institute for Minority Health and Health Disparities (NIMHD) [HHS - NIH]

National Institute of Neurological Disorders and Stroke (NNDS) [HHS - NIH]

Trumbull, Connecticut 066114874 United States

Single Zip Code

HEAL INITIATIVE: Development of Therapies and Technologies Directed at Enhanced Pain Management (R43/R44 - Clinical Trial Required) (RFA-NS-20-010)

Amendment Since initial award the total obligations have increased 205% from $1,482,405 to $4,518,543.