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Multimodal Biomarkers for Diagnosis and Prognosis in CAA (CAA)

Primary Purpose

Cerebral Amyloid Angiopathy, Intracranial Hemorrhages, Alzheimer Disease

Status

Unknown status

Phase

Phase 3

Locations

Taiwan

Study Type

Interventional

Intervention

1. amyloid PET；2. T807 PET

About this trial

This is an interventional diagnostic trial for Cerebral Amyloid Angiopathy focused on measuring Stroke, intracerebral hemorrhage, cerebral amyloid angiopathy, amyloid PET, tau PET, MRI, Aβ, ApoE

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

ICH：
1. Age：above 20 years old.
2. Evidence of intraparenchymal hemorrhage on CT or MRI.
3. Patient agrees to participate in the study and receive neurophsychological examinations, genetic and biochemical markers test, MRI and PET imaging.
AD：
1. Age：above 20 years old.
2. Patients who fulfills the clinical criteria of possible or probable Alzheimer's disease (AD).51
3. Patient agrees to participate in the study and receive neurophsychological examinations, genetic and biochemical markers test, MRI and PET imaging.
Control：
1. Age：above 20 years old.
2. Patient agrees to participate in the study and receive neurophsychological examinations, genetic and biochemical markers test, MRI and PET imaging.

Exclusion Criteria:

ICH：
1. patients with potential causes of hemorrhage including trauma, structural lesion, brain tumor, or coagulopathy due to systemic disease or medication.
2. 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.
3. Patients with pregnancy or recently having a plan for pregnancy.
4. Patients with breast feeding or recently having a plan for breast feeding.
5. Patients with history of allergy to 11C-PiB and 18F-T807, or severe allergy history.
6. Patient or family who does not agree to participate in the study.
7. patient with high risk by doctor evaluate.
AD：
1. 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.
2. Patients with pregnancy or recently having a plan for pregnancy.
3. Patients with breast feeding or recently having a plan for breast feeding.
4. Patients with history of allergy to 11C-PiB and 18F-T807, or severe allergy history.
5. Patient or family who does not agree to participate in the study.
6. patient with high risk by doctor evaluate.
Control：
1. History of neurological or psychiatric disease, abnormal neurological examination.
2. 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.
3. Patients with pregnancy or recently having a plan for pregnancy.
4. Patients with breast feeding or recently having a plan for breast feeding.
5. Patients with history of allergy to 11C-PiB and 18F-T807, or severe allergy history.
6. Patient or family who does not agree to participate in the study.
7. patient with high risk by doctor evaluate.

Sites / Locations

National Taiwan Univeristy HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

amyloid PET、T807 PET

Arm Description

PET/CT

Outcomes

Primary Outcome Measures

PET imaging

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT03969732

First Posted

May 29, 2019

Last Updated

March 10, 2021

Sponsor

National Taiwan University Hospital

1. Study Identification

Unique Protocol Identification Number

NCT03969732

Brief Title

Multimodal Biomarkers for Diagnosis and Prognosis in CAA

Acronym

CAA

Official Title

Multimodal Biomarkers for Diagnosis and Prognosis in Cerebral Amyloid Angiopathy

Study Type

Interventional

2. Study Status

Record Verification Date

March 2021

Overall Recruitment Status

Unknown status

Study Start Date

September 27, 2018 (Actual)

Primary Completion Date

July 31, 2022 (Anticipated)

Study Completion Date

July 31, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Taiwan University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

By combination of plasma (Aβ40, Aβ42, total tau, and phosphorylated tau, etc.), genetic (ApoE ε2 or ε4 allele), MRI (cerebral perfusion, microbleeds, cortical superficial siderosis, enlarged perivascular space, etc.) and PET imaging (amyloid and tau) biomarkers, the study aims to Enhance the diagnostic potentials of the radiological biomarkers by combining MRI and amyloid PET in CAA patients. Investigate the biological pathogenesis in CAA patients using the less invasive plasma biomarkers and to correlate with structural and function imaging, including MRI, amyloid and tau imaging. Study the characteristics of long-term progression of amyloid deposition in CAA patients using the radiological, biochemical and genetic biomarkers. Study the prognosis predicting markers.

Detailed Description

Intracranial hemorrhage (ICH) consists of about a quarter of stroke subtype. For elderly, cerebral amyloid angiopathy (CAA) is a common etiology of ICH. In National Taiwan University Hospital, we have established a CAA team including neurologists, radiologists and nuclear medicine physicians since 2014. We hope to go deep into the diagnosis and pathophysiology of CAA. To the best of our knowledge, there is no other CAA team in Taiwan. In patients with CAA, abnormal beta amyloid protein diffusely deposits at cerebral vasculatures, which disrupts the normal vessel structure and increases the risk of bleeding. The standard diagnosis for CAA requires pathological evidences of amyloid deposition at cerebral arteries. Clinically, a diagnosis of CAA-related ICH is usually only made in an elderly developing cortical or subcortical lobar ICH without undergoing biopsy. Brain images using the SWI sequence of MRI study may show lobar microbleeds in patients with CAA. However, there is still no direct and precise non-invasive diagnostic tool for CAA until now. Amyloid PET, using 11C-PiB to image amyloid burden, has been used for detecting the cerebral amyloid protein deposition in patients with Alzheimer's dementia (AD) for years. Recently, amyloid PET has also been applied in the diagnosis of CAA. CAA patients showed diffusely increased global PiB retention as compared to control subjects and the distribution of PiB retention is also different from that seen in patients with AD in general. Nevertheless, the applications of amyloid PET in CAA diagnosis are still not well established and many important issues still need to be extensively addressed. Furthermore, tau PET has emerged as a potential molecular imaging marker for SVD. Tau PET provides a noninvasive method for measuring brain tau load. The correlation of tau PET findings in patients with CAA has not been investigated before. In addition, ApoE gene has been reported to be risk factor for sporadic CAA as well as AD. Biochemical biomarkers, such as the levels of Aβ40 and Aβ42, also help us understand the pathophysiology of CAA. Recently, immunomagnetic reduction (IMR) assay, using bio-functionalized magnetic nanoparticles, has been proved to be a sensitive and accurate tool for the detection of these biological molecules. By combination of plasma (Aβ40, Aβ42, total tau, and phosphorylated tau, etc.), genetic (ApoE ε2 or ε4 allele), MRI (cerebral perfusion, microbleeds, cortical superficial siderosis, enlarged perivascular space, etc.) and PET imaging (amyloid and tau) biomarkers, the study aims to Enhance the diagnostic potentials of the radiological biomarkers by combining MRI and amyloid PET in CAA patients. Investigate the biological pathogenesis in CAA patients using the less invasive plasma biomarkers and to correlate with structural and function imaging, including MRI, amyloid and tau imaging. Study the characteristics of long-term progression of amyloid deposition in CAA patients using the radiological, biochemical and genetic biomarkers. Study the prognosis predicting markers.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cerebral Amyloid Angiopathy, Intracranial Hemorrhages, Alzheimer Disease

Keywords

Stroke, intracerebral hemorrhage, cerebral amyloid angiopathy, amyloid PET, tau PET, MRI, Aβ, ApoE

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

240 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

amyloid PET、T807 PET

Arm Type

Experimental

Arm Description

PET/CT

Intervention Type

Drug

Intervention Name(s)

1. amyloid PET；2. T807 PET

Intervention Description

Dynamic PET acquisition for 60 minutes will be acquired after injection of 10 mCi 11C-PiB (39 frames: 8 x 15 seconds, 4 x 60 seconds, 27 x120 seconds). Dynamic PET imaging 3D acquisition will be acquired 80 minutes after injection of 10 mCi 18F-T807 (4 x 300 seconds)

Primary Outcome Measure Information:

Title

PET imaging

Description

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.

Time Frame

in 3 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: ICH： 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. AD： Age：above 20 years old. Patients who fulfills the clinical criteria of possible or probable Alzheimer's disease (AD).51 Patient agrees to participate in the study and receive neurophsychological examinations, genetic and biochemical markers test, MRI and PET imaging. Control： Age：above 20 years old. Patient agrees to participate in the study and receive neurophsychological examinations, genetic and biochemical markers test, MRI and PET imaging. Exclusion Criteria: ICH： 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. AD： 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. Control： History of neurological or psychiatric disease, abnormal neurological examination. 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.

Facility Information:

Facility Name

National Taiwan Univeristy Hospital

City

Taipei

ZIP/Postal Code

100

Country

Taiwan

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yen Ruoh Fang, MD, PhD

Phone

886-2-23123456

Ext

65581

rfyen@ntu.edu.tw

12. IPD Sharing Statement

Plan to Share IPD

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Multimodal Biomarkers for Diagnosis and Prognosis in CAA

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