R01NS120557

Repeated Assessment of Survivors in ICH (REASSESS ICH) - Project Summary / Abstract

Purpose:
The Repeated Assessment of Survivors in ICH study will conduct long-term cognitive, functional, and neuropsychiatric performance assessments to determine if evacuation of spontaneous intracerebral hemorrhage (ICH) reduces the risk of later cognitive decline in the aging brain. This study will compare rates of cognitive decline under two treatment strategies for intracerebral hemorrhage: the use of minimally invasive surgery with two similar techniques as performed in the recently completed MISTIE III and ENRICH trials, and the current standard of care using data from both controls in MISTIE III and ENRICH and comparative data from the Ethnic/Racial Variations of ICH (ERICH) study (U-01-NS067963) extended into the ERICH-Longitudinal Study (R01-NS093870) which followed over 900 of the cases with serial cognitive examinations.

Rationale:
Intracerebral hemorrhage has the highest disability rate among stroke survivors. ICH survivors are at particularly high risk for progressive cognitive impairment which is strongly associated with greater hematoma volume, but also with cerebral amyloid angiopathy. Compared with standard of care, minimally invasive surgery with effective hematoma volume reduction may improve long-term functional outcomes while also reducing mortality. As such, reducing hematoma volume after ICH may reduce the risk of post ICH cognitive decline.

Design:
REASSESS ICH is a longitudinal structured serial telephone interview follow-up plus one-time in-person visit of an anticipated 359 ICH survivors enrolled in MISTIE III (2013-2017) or ENRICH (2018-2022). Cognitive and functional outcome data will be compared with up to 900 patients enrolled in ERICH-L, to determine if surgical ICH reduction leads to reduced risk of progressive cognitive decline.

Primary Aim 1:
To determine if surgical clot reduction after ICH reduces the risk of progressive cognitive decline.

Hypothesis:
The final residual volume of ICH will correlate with risk of cognitive decline after controlling for age, sex, initial volume of ICH, leukoaraiosis, APOE genotype, and hypertension treatment among operated and non-operated survivors of MISTIE III/ENRICH and survivors of ERICH, and effective clot reduction (<20 mL end of treatment volume), will be associated with lower risk of cognitive decline compared to non-operated patients.

Primary Aim 2:
To determine if there is a long-term benefit in survival and functional outcome from minimally invasive surgery and the interaction with cognitive decline.

Hypothesis:
Effective clot reduction will be associated with a decreased risk of death/major disability compared to non-operated patients.

Exploratory Aim 3:
To determine if inflammatory gene pathway expression predicts risk of cognitive decline.

Hypothesis:
Chronic brain inflammation contributes to progressive cognitive impairment post ICH. Our preliminary data identifies that inflammation appears to occur chronically after ICH; not just acutely. When testing a wide variety of gene expression changes, the context of which pathway is involved is critical to provide context. We will evaluate whether inflammatory pathways in particular predict patients with cognitive impairment independent of gene risk scores for dementia and surgical status.

The Johns Hopkins University

(1) TO SUPPORT EXTRAMURAL RESEARCH FUNDED BY THE NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE (NINDS) INCLUDING: BASIC RESEARCH THAT EXPLORES THE FUNDAMENTAL STRUCTURE AND FUNCTION OF THE BRAIN AND THE NERVOUS SYSTEM, RESEARCH TO UNDERSTAND THE CAUSES AND ORIGINS OF PATHOLOGICAL CONDITIONS OF THE NERVOUS SYSTEM WITH THE GOAL OF PREVENTING THESE DISORDERS, RESEARCH ON THE NATURAL COURSE OF NEUROLOGICAL DISORDERS, IMPROVED METHODS OF DISEASE PREVENTION, NEW METHODS OF DIAGNOSIS AND TREATMENT, DRUG DEVELOPMENT, DEVELOPMENT OF NEURAL DEVICES, CLINICAL TRIALS, AND RESEARCH TRAINING IN BASIC, TRANSLATIONAL AND CLINICAL NEUROSCIENCE. THE INSTITUTE IS THE LARGEST FUNDER OF BASIC NEUROSCIENCE IN THE US AND SUPPORTS RESEARCH ON TOPICS INCLUDING BUT NOT LIMITED TO: DEVELOPMENT OF THE NERVOUS SYSTEM, INCLUDING NEUROGENESIS AND PROGENITOR CELL BIOLOGY, SIGNAL TRANSDUCTION IN DEVELOPMENT AND PLASTICITY, AND PROGRAMMED CELL DEATH, SYNAPSE FORMATION, FUNCTION, AND PLASTICITY, LEARNING AND MEMORY, CHANNELS, TRANSPORTERS, AND PUMPS, CIRCUIT FORMATION AND MODULATION, BEHAVIORAL AND COGNITIVE NEUROSCIENCE, SENSORIMOTOR LEARNING, INTEGRATION AND EXECUTIVE FUNCTION, NEUROENDOCRINE SYSTEMS, SLEEP AND CIRCADIAN RHYTHMS, AND SENSORY AND MOTOR SYSTEMS. IN ADDITION, THE INSTITUTE SUPPORTS BASIC, TRANSLATIONAL AND CLINICAL STUDIES ON A NUMBER OF DISORDERS OF THE NERVOUS SYSTEM INCLUDING (BUT NOT LIMITED TO): STROKE, TRAUMATIC INJURY TO THE BRAIN, SPINAL CORD AND PERIPHERAL NERVOUS SYSTEM, NEURODEGENERATIVE DISORDERS, MOVEMENT DISORDERS, BRAIN TUMORS, CONVULSIVE DISORDERS, INFECTIOUS DISORDERS OF THE BRAIN AND NERVOUS SYSTEM, IMMUNE DISORDERS OF THE BRAIN AND NERVOUS SYSTEM, INCLUDING MULTIPLE SCLEROSIS, DISORDERS RELATED TO SLEEP, AND PAIN. PROGRAMMATIC AREAS, WHICH ARE PRIMARILY SUPPORTED BY THE DIVISION OF NEUROSCIENCE, ARE ALSO SUPPORTED BY THE DIVISION OF EXTRAMURAL ACTIVITIES, THE DIVISION OF TRANSLATIONAL RESEARCH, THE DIVISION OF CLINICAL RESEARCH, THE OFFICE OF TRAINING AND WORKFORCE DEVELOPMENT, THE OFFICE OF PROGRAMS TO ENHANCE NEUROSCIENCE WORKFORCE DEVELOPMENT, AND THE OFFICE OF INTERNATIONAL ACTIVITIES. (2) TO EXPAND AND IMPROVE THE SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. TO UTILIZE THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM, TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.866 - Aging Research

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

National Institute on Aging (NIA) [HHS - NIH]

Maryland United States

State-Wide

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 667% from $979,826 to $7,516,765.