Clinical trial NCT06836141: Biomarkers for Cognitive Decline in Intracerebral Hemorrhage
Official title: Silent Brain Infarcts in Spontaneous Intracerebral Hemorrhage as a Prognostic Biomarker for Vascular Contributions to Cognitive Impairment and Dementia (VCID)
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Primary Intracerebral Hemorrhage
Lead sponsor: Rush University Medical Center
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2025-02-20
Enrollment: 118
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients admitted to Rush University Medical Center with an intracerebral hemorrhage.

Brief summary: The goal of this clinical trial is to see if silent brain infarcts (SBIs), or stroke-like symptoms detectable during brain imaging, are a possible contributor to cognitive decline for patients diagnosed with spontaneous intracerebral hemorrhage (sICH), or blood clot in the brain. The main questions it aims to answer are

* if SBIs in sICH are associated with a lower cognitive level and more rapid cognitive decline
* if SBIs in sICH are associated with certain findings on brain imaging
* if SBIs in sICH are associated with higher inflammation measured by certain blood tests

Participants will undergo

* cognitive testing during hospitalization, and at 3, 6 and 12 months after the sICH
* Magnetic Resonance Imaging (MRI) of the brain during hospitalization and 12 months after the sICH
* blood draws during hospitalization and at 3, 6 and 12 months after the sICH

Detailed description: This proposal's objective is to establish SBIs (silent brain infarct) as an early, pathophysiologically plausible neuroimaging biomarker for VCID (vascular contributions to cognitive impairment and dementia) in sICH (spontaneous intracerebral hemorrhage) patients. To attain the overall objective, we will recruit a cohort of 118 sICH participants over 3 years and longitudinally measure cognitive function, WMH volumetric progression, and serum suPAR levels. Aim #1: To test the hypothesis that SBIs in sICH are associated with a lower cognitive level and more rapid cognitive decline. Approach: In sICH patients with and without SBIs, we will compare global cognition (primary analysis) and multiple cognitive domains (secondary analysis) at hospitalization, and at 3 months, 6 months, and 12 months after discharge using a comprehensive cognitive battery. Aim #2: To test the hypothesis that SBIs in sICH are associated with more rapid WMH (white matter hyperintensities) progression as measured by serial MRI (magnetic resonance imaging). Approach: In sICH patients with and without SBIs, we will compare the absolute volumetric change in WMH using a novel imaging analysis algorithm on serial 3-Tesla brain MRI at hospitalization and at 12 months after discharge. Aim #3: To test the hypothesis that SBIs in sICH are associated with higher chronic systemic inflammation as measured by serum suPAR. Approach: In sICH patients with and without SBIs, we will compare serum levels of suPAR at hospitalization, and at 3 months, 6 months, and 12 months after discharge.

This study will be a prospective longitudinal study of sICH patients comparing those with and without SBIs. All patients with primary sICH are admitted to Rush University Medical Center's (RUMC) Neurosciences Intensive Care Unit and managed by a multi-disciplinary team of neurologists and neurosurgeons according to a standardized protocol based on current guidelines. Primary sICH will be defined as either hypertensive or related to cerebral amyloid angiopathy as diagnosed using the Boston Criteria version 2.0. This differs from secondary sICH, defined as hemorrhage due to vascular malformation, coagulopathy, trauma, malignancy, or reversible vasculopathy. Before hospital discharge, participants will receive baseline cognitive testing, MRI brain, and suPAR (soluble urokinase-type plasminogen activator receptor) serology sampling. After discharge from the hospital, participants will follow up in RUMC's Comprehensive Stroke Clinic at 3 months as part of their routine stroke care per our center's protocol. At the 3-month visit, participants will receive cognitive testing and provide suPAR serology. Participants will complete an interim 6-month visit with cognitive testing and suPAR serology. At a 12-month research clinic visit, participants will repeat cognitive testing, brain MRI, and suPAR serology. All participant encounters will provide the opportunity to gather interim clinical data such as new medical diagnoses or repeat hospitalizations.

Eligibility criteria: Inclusion Criteria:

* Primary Intracerebral Hemorrhage
* Age ≥ 18 and \< 80 years

Exclusion Criteria:

* ICH score \> 2
* Pre-existing dementia
* Prior history of stroke
* Neurosurgical evacuation of hematoma

Primary outcomes:
measure: Global Cognition
timeFrame: From date of randomization and assessed throughout the during hospitalization for qualifying ICH event up to 12 months
measure: Global Cognition
timeFrame: 3 months after hospitalization
measure: Global Cognition
timeFrame: 6 months after hospitalization
measure: Global Cognition
timeFrame: 12 months after hospitalization
measure: Absolute volumetric change in White Matter Hyperintensity (WMH)
timeFrame: from MRI at hospitalization to MRI at 12 months
measure: Serum soluble urokinase-type plasminogen activator receptor (suPAR) levels
timeFrame: From date of consent and assessed during hospitalization for qualifying ICH event up to 12 months
measure: Serum soluble urokinase-type plasminogen activator receptor (suPAR) levels
timeFrame: 3 months after hospital discharge
measure: Serum soluble urokinase-type plasminogen activator receptor (suPAR) levels
timeFrame: 6 months after hospital discharge
measure: Serum soluble urokinase-type plasminogen activator receptor (suPAR) levels
timeFrame: 12 months after hospital discharge
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
Study officials:
affiliation: Rush University Medical Center
name: Rajeev Garg, MD
role: PRINCIPAL_INVESTIGATOR
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