ASPIRE

Stroke, the third leading cause of death and the leading cause of adult disability in the United States, has a disproportionate impact on underserved populations that is reflected in higher incidence and mortality rates in these groups. Several studies have suggested that blacks are less likely than whites to receive intravenous tissue plasminogen activator (IV tPA), the only FDA-approved acute ischemic stroke therapy. Efforts are needed to elucidate factors contributing to racial/ethnic disparities in access to acute stroke care and to develop programs to overcome these barriers. The specific aims of this intervention project are: A) to identify previously unrecognized sociocultural and environmental barriers to acute stroke treatment in an underserved, urban population; B) to investigate whether implementation of a multilevel intervention designed to address these barriers can significantly increase the number of ischemic stroke patients appropriately treated with intravenous tissue plasminogen activator (IV tPA); and C) to perform program evaluation of the methods used in the intervention to determine which efforts are the most effective. The investigators will assist each of 6 hospitals in the District of Columbia to develop a team of Stroke Champions to implement educational programs and standardized procedures designed to improve acute stroke care. Five Baltimore hospitals will serve as the control group. Essential design features of this project include: 1) a focus on underserved populations to identify community-specific barriers and then tailor existing stroke education materials to increase health literacy and decrease delays in seeking treatment; 2) implementation of interventions to address educational, attitudinal, and structural barriers at the public, paramedic and hospital levels; and 3) assignment of a dedicated research coordinator to each hospital who will also serve as a Stroke Champion. The long term objective of the trial is to identify systematic, reproducible, effective methods for improving the delivery of acute stroke therapies in underserved areas that can be implemented in a broader arena. The only way to definitively affect outcomes for underserved stroke patients is to elucidate the complex issues related to access to treatment, and the District of Columbia is the ideal city in which to perform these investigations.

PROTECT DC

Inadequate control of vascular risk factors contributes to health disparities, particularly in secondary stroke prevention. PROTECT DC is a randomized phase II intervention clinical trial designed to determine whether hospital-based initiation of secondary prevention strategies coupled with community-based case management (via “stroke navigators”) can improve secondary prevention measures in underserved patients. PROTECT DC is adapted from the Stroke PROTECT (Preventing Recurrence Of Thromboembolic Events through Coordinated Treatment) program, which systematically implements medication/behavioral secondary prevention measures. The general aim of this proposal is to prepare for a future Phase III trial of the PROTECT DC intervention: an in-hospital education coupled with community-based “stroke navigators” designed to reduce the rate of vascular events or death in a population of underserved stroke patients. The current proposed phase II study will employ surrogate measures of risk factor control to detect a signal of efficacy from the PROTECT DC intervention. The two specific aims are to: 1) assess the effect of PROTECT DC on four objective markers of secondary stroke risk factor control (antithrombotic therapy, antihypertensive therapy, lipid-lowering medication, and anti-diabetic medication) in patients randomized to PROTECT DC vs. those randomized to an observational control, and 2) assess the contribution of health status, depression, cognition, socio-economic status, race and other factors to the incidence of barriers and the rate of response to the study interventions. A total of 250 primarily inner-city, underserved, ischemic stroke patients will be recruited from 2 DC hospitals: Howard University Hospital and Washington Hospital Center. Patients will be randomized to the PROTECT DC intervention (hospital based secondary prevention education plus community-based stroke navigators for one year) vs. standardized usual and customary care for one year. The primary endpoint is secondary stroke risk factor control for the 4 medication goals as determined by normalization of target laboratory values (systolic blood pressure, LDL, Hemoglobin A1c) or pill count for the antiplatelet goal. Secondary endpoints include rates of vascular events, functional status and a variety of disability, quality of life, and social participation measures. PROTECT DC intervention will be further refined by reviewing and adapting culturally sensitive educational materials for PROTECT DC; determining the frequency of modifiable and non-modifiable specific barriers to compliance; refining and standardizing strategies to overcome identified barriers to compliance; and refining materials and programs to train and supervise stroke navigators. The work proposed is expected to lead to a Phase III trial adequately powered to demonstrate the effectiveness of PROTECT DC in reducing recurrent vascular event rates in underserved populations.

DECIPHER

The overall goal of DECIPHER is to investigate whether racial/ethnic differences exist in the underlying risk factors for chronic cerebral microbleeds in patients with primary ICH and to determine the prognostic impact of microbleeds in a predominantly underserved ICH population. Intracerebral hemorrhage (ICH) is a devastating and disabling disease with 30 day mortality rates estimated at 35-52%. Primary ICH is 2-3 times more common in many underserved populations, including blacks. Hypertension and cerebral amyloid angiopathy have been identified as common risk factors for primary ICH in the general population. Microbleeds, clinically silent small, chronic hemorrhages identified on gradient echo (GRE) MRI, are present in approximately 70% of patients with primary ICH and are hypothesized to be a marker of a hemorrhage-prone vasculopathy. In patients with cerebral amyloid angiopathy, the number of microbleeds has significant prognostic value, predicting future risk of ICH, poor long-term neurologic outcome, and cognitive decline. Our recent pilot data suggest that black patients presenting with ICH have a significantly greater number of chronic microbleeds compared to whites. However, the underlying etiology and significance of this finding are unknown. The 4 specific aims of this longitudinal, MR imaging cohort study are: 1) To quantify by race/ethnicity the prevalence, lesion burden and risk factors of chronic cerebral microbleeds in patients with primary ICH; 2) To quantify the prognostic impact of initial microbleed burden by race/ethnicity; 3) To quantify the long-term rate of development of new microbleeds by race/ethnicity and to correlate this rate with neurologic and functional outcome; and 4) To perform a genetic substudy to explore genetic risk factors for ICH and microbleeds in this underserved population. A total of 189 patients with primary ICH will be enrolled and followed for up to 4 years. Repeat MRIs including GRE sequences will be performed at years 1 and 3 and evaluated for progression of disease (new microbleeds, recurrent ICH, ischemic stroke, and leukoaraiosis). Additional measures to be evaluated will include demographic information, presence and control of vascular risk factors including hypertension, apolipoprotein E status, and functional outcome. This project will not only provide insight into the significance of microbleeds in underserved ICH populations, but will also provide pilot data for design of future intervention trials of secondary prevention measures.

Administration Core

The administrative core provides administrative management of the program grant. Dr. Kidwell, the program Director, assumes the primary responsibility for program leadership and management. This core is responsible for overseeing the day-to-day operations of the program including management of budgets and subcontracts, organization of meetings and conference calls, and circulating communications amongst participants. Dr. Kidwell has been assisted by the Scientific Advisory Committee (SAC) comprised of the project Principal and Co-Investigators. This central administrative and leadership unit will be responsible for determining the vision, priorities and principal functions of the program as a whole and for developing an interdisciplinary research environment to facilitate the missions of the individual Cores and Projects. In addition, this administrative group will enhance and facilitate interactions between the Cores and Projects, and between the Georgetown coordinating center, affiliate institutions, the Washington DC community, and NIH-NINDS. The administrative core will also oversee the training and career development component of the grant that provides relevant research training to undergraduate, graduate and medical students, and postdoctoral fellows with an emphasis on research addressing stroke disparities. The members of the SAC will meet at least monthly throughout the award period to review the program’s activities, set priorities, and ensure continuous total quality management of the overall program. A Program Advisory Committee (PAC), comprised of international experts in neuroscience and epidemiologic research, advises the SAC on scientific aspects of the project and meets annually to review and assess overall research performance.

PRRIO Core

The Patient Recruitment Retention, Intervention and Outcomes Core (RRRIO) guides outreach and tailored stroke education to high risk communities in the District of Columbia, facilitate recruitment and retention of study participants, develop and refine behavioral interventions, evaluate the effectiveness of community programs aimed at decreasing barriers to acute stroke treatment, and assess outcomes of participants enrolled in Projects 2 and 3. Dr. Edwards, the Core PI, will be assisted in achieving these aims by Dr. Gibbons, the Co-PI, and Dr. Covington, a Co-investigator. This Core is responsible for cultural sensitivity training of investigators and all project staff, development and review of recruitment, consent and participant education materials and procedures, and collection of program evaluation and functional outcome data. The Core Investigators interact with and support the activities of Projects 1, 2, and 3 as well as assist Core C with the scoring, analysis and interpretation of outcome data. Drs. Edwards and Gibbons will design and implement community surveys, focus groups and key informant interviews to identify barriers to acute stroke treatment with Dr. Kidwell, PI of Project 1. Dr. Covington assists Dr. Kidwell with the training of students from Georgetown and Howard Universities as stroke ambassadors. Dr. Covington and Dr. Edwards co-facilitate regular meetings of the Community Advisory Committee. Drs. Gibbons and Covington assist Dr. Dromerick, PI of Project 2, in the training and day to day supervision of stroke navigators. Dr. Covington will supervise day to day data collection activities. The Core investigators will hold a weekly teleconference and communicate via email and telephone on a day to day basis as needed. The overall goal of the PRRIO Core is to provide information on the elimination of barriers to effective treatment and the impact of health disparities on long term stroke outcomes. The PRRIO Core supports the translation of the Stroke Disparities Program Project findings to more effective stroke prevention, evidence-based treatment and secondary prevention programs for underserved racial/ethnic populations.

BDM Core

The Biostatistics and Data Management Core (Core C) provides integrated statistical and technical support to all projects under the Stroke Disparities Program (SDP). Core C is housed in the Department of Biostatistics and Epidemiology of the MedStar Health Research Institute, located in Washington, DC, and is in close proximity to the SDP investigative team and the hospitals involved in SDP studies. The aims of Core C are: 1) To provide consultation on study design, study logistics and integration of studies across the SDP program (Study Design); 2) To provide data management to all SDP projects (Data Management); 3) To coordinate review and approval of analytical plans (Statistical Planning and Review); and 4) To conduct statistical analysis, interpret study data, participate in writing of manuscripts and facilitate distribution of SDP data to the scientific community (Data Analysis and Distribution). Core C engages in ongoing scientific discussions with SDP Core and Project PIs to ensure smooth and sound implementation of projects under the SDP umbrella. Core C's data collection and manageent plans involve designing, testing and deploying web-based data systems for each of the SDP projects. These systems include numerous quality control features, as well as randomization functions for appropriate projects. Core C produces study documentation such as codebooks, annotated data collection forms, conduct regular audits of the clinical sites. Core C generates recruitment and retention reports for the projects as well as conduct interim analyses where appropriate. The Core participates actively in the Publications Committee of SDP, providing statistical review and oversight during the review of proposals and completed manuscripts. Core C provides centralized statistical analytic support for the entire SDP program by conducting data analysis in collaboration with SDP writing groups, and participate in manuscript preparation. To encourage data sharing and collaboration, Core C will produce public use data sets with accompanying documentation and deliver these materials to the NIH/NINDS data repository at the end of the study period. Core C interacts with Cores A and B in numerous ways, such as collaborative work on the Publications Committee and collaborative efforts on coding and derivation of stroke-specific variables and summary scales. Core C is experienced in provision of data management and statistical support for NIH-funded studies of diabetes and cardiovascular disease, with a particular emphasis on minority health, health disparities and clinical trials of cardiovascular disease. This experience will be applied to stroke disparities as part of a comprehensive program of technical and scientific support to the SDP program.