Biomarkers for Cognitive Decline in Intracerebral Hemorrhage

Официальное название

Silent Brain Infarcts in Spontaneous Intracerebral Hemorrhage as a Prognostic Biomarker for Vascular Contributions to Cognitive Impairment and Dementia (VCID)

Обзор

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

Подробное описание

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.

Вмешательства

• Диагностический тест MRI
  MRI during hospitalization and at 12 months post sICH
• Диагностический тест Blood Draw
  Will occur during hospitalization and at 3, 6 and 12 months post sICH
• Диагностический тест Cognitive Test
  Cognitive testing will occur during hospitalization and at 3, 6 and 12 months post sICH

Первичные конечные точки

• Global Cognition [Срок оценки: From date of randomization and assessed throughout the during hospitalization for qualifying ICH event up to 12 months]
• Global Cognition [Срок оценки: 3 months after hospitalization]
• Global Cognition [Срок оценки: 6 months after hospitalization]
• Global Cognition [Срок оценки: 12 months after hospitalization]
• Absolute volumetric change in White Matter Hyperintensity (WMH) [Срок оценки: from MRI at hospitalization to MRI at 12 months]
• Serum soluble urokinase-type plasminogen activator receptor (suPAR) levels [Срок оценки: From date of consent and assessed during hospitalization for qualifying ICH event up to 12 months]
• Serum soluble urokinase-type plasminogen activator receptor (suPAR) levels [Срок оценки: 3 months after hospital discharge]
• Serum soluble urokinase-type plasminogen activator receptor (suPAR) levels [Срок оценки: 6 months after hospital discharge]
• Serum soluble urokinase-type plasminogen activator receptor (suPAR) levels [Срок оценки: 12 months after hospital discharge]

Критерии участия

Критерии включения

• Primary Intracerebral Hemorrhage
• Age ≥ 18 and < 80 years

Критерии исключения

• Pre-existing dementia

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

США · 1 центр

• Rush University Medical Center — Chicago

Публикации

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• Hemorrhagic Stroke Academia Industry (HEADS) Roundtable Participants; Second HEADS Roundtable Participants. Recommendations for Clinical Trials in ICH: The Second Hemorrhagic Stroke Academia Industry Roundtable. Stroke. 2020 Apr;51(4):1333-1338. doi: 10.1161/STROKEAHA.119.027882. Epub 2020 Feb 10. No abstract available. PMID 32078490
• Hwang DY, Kim KS, Muehlschlegel S, Wartenberg KE, Rajajee V, Alexander SA, Busl KM, Creutzfeldt CJ, Fontaine GV, Hocker SE, Madzar D, Mahanes D, Mainali S, Sakowitz OW, Varelas PN, Weimar C, Westermaier T, Meixensberger J. Guidelines for Neuroprognostication in Critically Ill Adults with Intracerebral Hemorrhage. Neurocrit Care. 2024 Apr;40(2):395-414. doi: 10.1007/s12028-023-01854-7. Epub 2023 No PMID 37923968
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• Wilson RS, Yu L, Lamar M, Schneider JA, Boyle PA, Bennett DA. Education and cognitive reserve in old age. Neurology. 2019 Mar 5;92(10):e1041-e1050. doi: 10.1212/WNL.0000000000007036. Epub 2019 Feb 6. PMID 30728309
• Garg RK, Khan J, Dawe RJ, Conners J, John S, Prabhakaran S, Kocak M, Bhabad S, Simpson SL, Ouyang B, Jhaveri M, Bleck TP. The Influence of Diffusion Weighted Imaging Lesions on Outcomes in Patients with Acute Spontaneous Intracerebral Hemorrhage. Neurocrit Care. 2020 Oct;33(2):552-564. doi: 10.1007/s12028-020-00933-3. PMID 32072457
• Grosu S, Rospleszcz S, Hartmann F, Habes M, Bamberg F, Schlett CL, Galie F, Lorbeer R, Auweter S, Selder S, Buelow R, Heier M, Rathmann W, Mueller-Peltzer K, Ladwig KH, Grabe HJ, Peters A, Ertl-Wagner BB, Stoecklein S. Associated factors of white matter hyperintensity volume: a machine-learning approach. Sci Rep. 2021 Jan 27;11(1):2325. doi: 10.1038/s41598-021-81883-4. PMID 33504924

Идентификаторы

NCT: NCT06836141 · 23022401 · 1R01NS135614-01A1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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