Cerebral Amyloid AngiopathyPhase 3CAANCT03969732
Multimodal Biomarkers for Diagnosis and Prognosis in CAA
A Phase 3 study testing 1. amyloid PET；2. T807 PET in people with Cerebral Amyloid Angiopathy and Intracranial Hemorrhages, run by National Taiwan University Hospital at 1 site in Taiwan.
Trial 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 1. Read more about this study
- Who is it for?
- Ages 20 years and olderHealthy volunteers can take part
- Conditions the study is for
- Cerebral Amyloid Angiopathy, Intracranial Hemorrhages, Alzheimer Disease
- What is being tested?
- 1. amyloid PET；2. T807 PET
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 240 participants
- Where
- 1 siteTaiwan
- Study dates
- 27 Sep 2018to 31 Jul 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
Taiwan1 site, 1 recruiting
- Recruiting
National Taiwan Univeristy Hospital
Taipei, 100
Yen Ruoh Fang, MD, PhD, 886-2-23123456 ext. 65581, rfyen@ntu.edu.tw
About this study
Official title: Multimodal Biomarkers for Diagnosis and Prognosis in Cerebral Amyloid Angiopathy
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.
Read the 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.
- Being tested
- 1. amyloid PET；2. T807 PET
- Keywords
- Stroke, intracerebral hemorrhage, cerebral amyloid angiopathy, amyloid PET, tau PET, MRI, Aβ, ApoE
- Medical subject headings
- Cerebral Amyloid Angiopathy, Intracranial Hemorrhages, Alzheimer Disease, Stroke, Cerebral Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
1. amyloid PET；2. T807 PETDrug
- 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)
| Study group | Role | What they receive |
|---|---|---|
| amyloid PET、T807 PET | Experimental | PET/CT Receives: Drug: 1. amyloid PET；2. T807 PET |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: in 3 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2019
- Study start27 Sep 2018
- Primary completion31 Jul 2022 (estimated)
- Study completion31 Jul 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cerebral Amyloid AngiopathyStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 240 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03969732
- Sponsor's protocol ID
- 201612094MINB
- Acronym
- CAA
- Status last verified
- Mar 2021
- First submitted
- 29 May 2019
- Last updated
- 12 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multimodal Biomarkers for Diagnosis and Prognosis in Cerebral Amyloid Angiopathy
- ClinicalTrials.gov ID
- NCT03969732
- Acronym / sponsor ID
- CAA / 201612094MINB
- Keywords
- Stroke, intracerebral hemorrhage, cerebral amyloid angiopathy, amyloid PET, tau PET, MRI, Aβ, ApoE
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 240 participants (estimated)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- 27 Sep 2018 (actual)
- Primary completion
- 31 Jul 2022 (estimated)
- Study completion
- 31 Jul 2022 (estimated)
- First posted
- 31 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| amyloid PET、T807 PET | Experimental | Drug: 1. amyloid PET；2. T807 PETPET/CT |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- ICH：
- AD：
- Control：
Key exclusion criteria (23 listed)
- ICH：
- AD：
- Control：
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 1. amyloid PET；2. T807 PET1. 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). 2. Dynamic PET imaging 3D acquisition will be acquired 80 minutes after injection of 10 mCi 18F-T807 (4 x 300 seconds) | Drug | amyloid PET、T807 PET |
Primary outcome
PET imaging
Time frame: in 3 days
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing 1. amyloid PET；2. T807 PET in people with Cerebral Amyloid Angiopathy and Intracranial Hemorrhages, run by National Taiwan University Hospital at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PET imaging (time frame: in 3 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2021.