- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04604587
MRI-visible Enlarged Perivascular Spaces and the Alteration of Lymphatic Drainage System in CAA (CAA)
MRI-visible Enlarged Perivascular Spaces and the Alteration of Lymphatic Drainage System in Cerebral Amyloid Angiopathy
Study Overview
Status
Intervention / Treatment
Detailed Description
Cerebral amyloid angiopathy (CAA) involves amyloid deposition in the vessel walls in the cerebral cortex and overlying leptomeninges, causing symptomatic intracerebral lobar intracerebral hemorrhage (ICH) in the elderly. CAA is considered as a form of cerebral small vessel disease, which refers to a group of vascular pathologies that affect the small vessels of the brain. In addition to lobar ICH, patients may present with other parenchymal injuries that can be detected on blood-sensitive MRI, such as multiple strictly lobar cerebral microbleeds, cortical superficial siderosis and leukoariosis. Recently, CAA has been suggested in association with MRI-visible enlarged perivascular space (EPVS) in centrum-semiovale (CSO), contrary to more severe MRI-visible EPVS in basal ganglia that is frequently found in chronic hypertension. The dilated perivascular space in CAA is suggestive of chronic poor perivascular drainage of the leptomeningeal arteries, predisposing individuals to impaired or altered meningeal lymphatic drainage and causing defect in amyloid clearance and subsequent CAA development. Nevertheless, it is unknown whether lymphatic drainage are the main routes for vascular amyloid clearance, and its relationship to the long-term outcome has not been clearly investigated in clinical patients yet.
In this three-year proposal, we will explore the MRI-visible EPVS in CAA and investigate its pathophysiology using animal models. Our specific aims include: (1) Establish the relationship of MRI-visible enlarged perivascular space and CAA, (2) Determine whether vascular amyloid clearance in CAA is associated with lymphatic drainage system, (3) Establish longitudinal data for MRI-visible enlarged perivascular space and cerebral amyloid angiopathy progression. In the first year, we will recruit spontaneous ICH patients for brain MRI, in vivo amyloid imaging and measuring their plasma Aβ40/42 levels. We aim to confirm EPVS in CSO as a specific marker for CAA, and to provide direct evidence that dilated perivascular space is worse with more advanced CAA; For the second year, we plan to use transgenic CAA mouse models to confirm that meningeal lymphatic drainage routes are crucial for clearance of vascular amyloid-β. We will manipulate the lymphatic drainage routes by either blockage or enhancement of the lymphatic vessels, to see if the vascular amyloid clearance is affected; For the third year, the main research focus will on be establishing the longitudinal data on amyloid and tau deposition in clinical ICH patients. We plan to repeat in vivo amyloid imaging in 2 years, for the purpose of validating our hypothesis in human that baseline worse lymphatic drainage function is associated with quicker cerebral vascular amyloid progression or prediction of future CAA development. We will also recruit patients for in vivo tau imaging to investigate long-term neuronal injury and neurodegeneration, namely tau-mediated neurofibrillary tangle, in relation to the impaired perivascular drainage in CAA.
Study Type
Enrollment (Anticipated)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Taipei, Taiwan, 100
- Recruiting
- National Taiwan Univeristy Hospital
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Contact:
- Yen Ruoh Fang, MD, PhD
- Phone Number: 65581 886-2-23123456
- Email: rfyen@ntu.edu.tw
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age:above 20 years old.
- Evidence of intraparenchymal hemorrhage on CT or MRI.
- Patient agrees to participate in the study and receive neurophsychological examinations, genetic and biochemical markers test, MRI and PET imaging.
Exclusion Criteria:
- patients with potential causes of hemorrhage including trauma, structural lesion, brain tumor, or coagulopathy due to systemic disease or medication.
- Patients could not receive the PET and MRI studies, including but not limited to poor cooperative agitation impeding adequate study, allergy to contrast medium, hemodynamic instability, implantation of cardiac pacemaker, past history of receiving aneurysm clipping, panic mood to MRI study, impaired kidney function.
- Patients with pregnancy or recently having a plan for pregnancy.
- Patients with breast feeding or recently having a plan for breast feeding.
- Patients with history of allergy to 11C-PiB and 18F-T807, or severe allergy history.
- Patient or family who does not agree to participate in the study.
- patient with high risk by doctor evaluate.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: amyloid PET、T807 PET
PET/CT
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
PET imaging
Time Frame: in 3 days
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PET data will reconstruct with ordered set expectation maximization, corrected for attenuation, and each frame will be evaluated to verify adequate count statistics and absence of head motion.
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in 3 days
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Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Cardiovascular Diseases
- Vascular Diseases
- Metabolic Diseases
- Cerebrovascular Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Genetic Diseases, Inborn
- Proteostasis Deficiencies
- Metabolism, Inborn Errors
- Brain Diseases, Metabolic
- Brain Diseases, Metabolic, Inborn
- Cerebral Arterial Diseases
- Intracranial Arterial Diseases
- Intracranial Hemorrhages
- Cerebral Small Vessel Diseases
- Amyloidosis, Familial
- Hemorrhage
- Amyloidosis
- Cerebral Hemorrhage
- Cerebral Amyloid Angiopathy
- Cerebral Amyloid Angiopathy, Familial
Other Study ID Numbers
- 201912003MINC
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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