ROSE-Longitudinal Assessment With Neuroimaging

Recruiting

• Conditions: Intracerebral Hemorrhage

• Registration Number: NCT05089331
• Lead Sponsor: University of Cincinnati

Brief Summary

The investigators will perform follow-up on 250 of 500 cases recruited into the ROSE study of cases with deep and lobar intracerebral hemorrhage to perform advanced neuroimaging at 12-24 months post stroke, and evaluations of motor and cognitive function at baseline, 6 months after baseline, and 12 months after baseline to determine predictors of recovery, progressive cognitive or functional impairment. The investigators propose to leverage the recruitment, DNA, RNA-seq and baseline advanced neuroimaging cohort of ROSE to obtain long-term neuroimaging and identical assessments longitudinally to address critical questions regarding the progressive decline of patients 12 to 24 months post intracerebral hemorrhage (ICH) with long term cognitive follow-up to 36 months on average. This proposal would represent the largest, and longest advanced neuroimaging and RNA-sequencing evaluation after ICH to date.

Detailed Description

The investigators propose to leverage the recruitment, DNA, RNA-seq and baseline advanced neuroimaging cohort of ROSE to obtain long-term neuroimaging and identical assessments longitudinally to address critical questions regarding the progressive decline of patients 12 to 24 months post ICH with long term cognitive follow-up to 36 months on average. This proposal would represent the largest, and longest advanced neuroimaging and RNA-sequencing evaluation after ICH to date.

Specific Aim #1: Determine if progressive cognitive impairment correlates with an increase in established markers of cerebral small vessel disease(CSVD) and cerebral amyloid angiopathy(CAA) (white matter disease, siderosis and microbleeds).

Hypothesis #1: Incidence of progressive cognitive impairment after ICH will be associated with an increase in total burden of small vessel disease (including white matter disease (WMD), microbleeds or siderosis, perivascular spaces, lacunar infarcts and atrophy).

Specific Aim #2: Determine if inflammation as measured by RNA-sequencing markers of inflammation correlates with progressive cognitive impairment.

Hypothesis #2: Interleukin-8 related inflammation will be associated with incidence of cognitive impairment.

Specific Aim #3: In this exploratory aim, we seek to identify novel neuroimaging markers associated with progressive cognitive decline.

Exploratory Hypothesis #3: Contralateral hemispheric diffusion tensor imaging (DTI) measures and cortical to cortical tract integrity will decline in association with progressive cognitive impairment.

Study Timeline

• Study Start: 2020-09-30
• Study First Submitted: 2021-10-11
• Study First Submitted QC: 2021-10-11
• Study First Posted: 2021-10-22
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-11
• Last Update Posted: 2023-05-12
• Primary Completion: 2024-09-30
• Study Completion: 2025-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 250

Inclusion Criteria

• Age 18 years or greater, fulfillment of the criteria for Deep, Subcortical or Lobar Intracerebral Hemorrhage
• No evidence of trauma, vascular malformation or aneurysm, or brain tumor as a cause of ICH.
• Ability of the patient or legal representative to provide informed consent

Exclusion Criteria

• Brainstem or Cerebellar ICH
• Patients Severely Affected by the ICH, Early Mortality, Hospice, or Withdraw of Care NOT eligible for ROS

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Determination of whether progressive cognitive impairment correlates with CVD and AA markers	Ongoing/completed by September 2024	Each subject has a baseline # Tesla (3T) MRI with DTI along with blinded central measurement of cerebral small vessel disease parameters. The current proposal is specifically designed to address these potential hypotheses by a comprehensive evaluation of detailed neurocognitive evaluations, baseline and long-term follow-up neuroimaging markers of CSVD and CAA as well as RNA sequencing of serum leukocytes for markers of inflammation.
Determination of whether inflammation as measured by RNA-sequencing markers of inflammation correlates with progressive cognitive impairment	Ongoing/completed by September 2024	The current proposal is specifically designed to address these potential hypotheses by a comprehensive evaluation of detailed neurocognitive evaluations, baseline and long-term follow-up neuroimaging markers of CSVD and CAA as well as RNA sequencing of serum leukocytes for markers of inflammation. If the occurrence of progressive cognitive decline is caused by inflammation from the ICH itself, those with cognitive decline should have chronically increased expression of inflammation compared to those without cognitive decline, where inflammatory markers normalize. Our preliminary data suggests a role of interleukin-8 as increased in expression after ICH.

Trial Locations

Locations (7)

Columbia University; 🇺🇸 New York, New York, United States

Baptist Health Louisville; 🇺🇸 Louisville, Kentucky, United States

University of Illinois Chicago; 🇺🇸 Chicago, Illinois, United States

Houston Methodist; 🇺🇸 Houston, Texas, United States

University of Maryland; 🇺🇸 Baltimore, Maryland, United States

University of Cincinnati; 🇺🇸 Cincinnati, Ohio, United States

Duke University; 🇺🇸 Durham, North Carolina, United States