Florbetaben as an Amyloid Plaque Marker in Elderly Patients With Focal or Disseminated Superficial Hemosiderosis

Study Overview
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Brief Summary
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The main objective of this study is to compare the distribution of Florbetaben (NEURACEQ: FBB) in the brain in amyloid cerebral angiopathy (ACA) manifested by isolated hemosiderosis in non-demented patients with that observed in healthy subjects, patients with ACA and with lobar hematoma(s) and patients with Alzheimer's dementia without MRI signs in favor of ACA.

Detailed Description
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The secondary objectives of this study are to compare among groups: A. The associated micro-bleeds. B. Associated leukoencephalopathy. C. Contrast observed in lobar Virchow-Robin perivascular spaces. D. Apolipoprotein E genotypes.

Official Title
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Evaluation of Florbetaben as an Amyloid Plaque Marker in Elderly Patients With Focal or Disseminated Superficial Hemosiderosis

Conditions
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Amyloid Cerebral Angiopathy, Alzheimer Disease

Intervention / Treatment
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* Device: Pet scan with FBB
* Device: MRI scan
* Biological: APO E genotyping


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for patients with amyloid cerebral angiopathy with isolated hemosiderosis: The patient must have given his/her informed and signed consent The patient must be insured or beneficiary of a health insurance plan The patient has a single or multiple focal spontaneous hemosiderosis objectified by an MRI The patient is does not have dementia (Mini Mental State score> 27) Inclusion Criteria for patients with amyloid cerebral angiopathy with with lobar hematoma(s): The patient must have given his/her informed and signed consent The patient must be insured or beneficiary of a health insurance plan The patient has one or more spontaneous lobar hematomas with or without hemosiderosis objectified by an MRI The patient is does not have dementia (Mini Mental State score> 27) Inclusion Criteria for patients with Alzheimer's type dementia without MRI signs in favor of amyloid cerebral angiopathy: The patient must have given his/her informed and signed consent The patient must be insured or beneficiary of a health insurance plan The patient has Alzheimer's dementia (Mini Mental State score <24) without hemosiderosis or previous lobar hematoma or history of other brain lesion seen on MRI Inclusion Criteria for health volunteers: The subject must have given his/her informed and signed consent The subject must be insured or beneficiary of a health insurance plan Healthy volunteers without cerebral neurological history and with normal MRI The subject is does not have dementia (Mini Mental State score> 27) Exclusion Criteria for patients with amyloid cerebral angiopathy with isolated hemosiderosis: The patient is participating in another interventional study The patient is in an exclusion period determined by a previous study The patient is under judicial protection The subject (next of kin or legal representative) refuses to sign the consent It is not possible to give the subject or his/her representative informed information The patient has an contra-indication for performing an MRI The patient is in the acute phase (the tracer does not bind in cases of large hematoma) Exclusion Criteria for patients with amyloid cerebral angiopathy with with lobar hematoma(s): The patient is participating in another interventional study The patient is in an exclusion period determined by a previous study The patient is under judicial protection The subject (next of kin or legal representative) refuses to sign the consent It is not possible to give the subject or his/her representative informed information The patient has an contra-indication for performing an MRI The patient is in the acute phase (the tracer does not bind in cases of large hematoma) Exclusion Criteria fpr patients with Alzheimer's type dementia without MRI signs in favor of amyloid cerebral angiopathy: The patient is participating in another interventional study The patient is in an exclusion period determined by a previous study The patient is under judicial protection The subject (next of kin or legal representative) refuses to sign the consent It is not possible to give the subject or his/her representative informed information The patient has an contra-indication for performing an MRI The patient is in the acute phase (the tracer does not bind in cases of large hematoma) Haemosiderosis or history of lobar hematoma or other visible cerebral history on MRI Exclusion Criteria for healthy volunteers: The subject is participating in another interventional study The subject is in an exclusion period determined by a previous study The subject is under judicial protection The subject (next of kin or legal representative) refuses to sign the consent It is not possible to give the subject or his/her representative informed information The subject has an contra-indication for performing an MRI Abnormal MRI The groups will be matched according to sex and age (by increments of 5 years) to the extent possible. Because amyloid cerebral angiopathy is a very rare condition, matching the two factors may be difficult to achieve. We therefore anticipate where appropriate to focus matching on age.

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: ACA with isolated hemosiderosis<br>This group is composed of patients with amyloid cerebral angiopathy (ACA) with isolated hemosiderosis. Intervention: Pet scan with FBB Intervention: MRI scan Intervention: APO E genotyping | Device: Pet scan with FBB<br>* Patients will have a pet scan with Florbetaben (NEURACEQ : FBB). All other care corresponds to routine care. Florbetaben is used during pet scans to visualize beta amyloid plaques and cannot be a separate intervention in and of itself.<br>Device: MRI scan<br>* Subjects will have an MRI scan at inclusion.<br>Biological: APO E genotyping<br>* Subjects will have APO (apolipoprotein) E genotyping if not already known.<br>|
| Other: ACA with lobar hematoma(s)<br>This group is composed of patients with amyloid cerebral angiopathy (ACA) with lobar hematoma(s). Intervention: Pet scan with FBB Intervention: MRI scan Intervention: APO E genotyping | Device: Pet scan with FBB<br>* Patients will have a pet scan with Florbetaben (NEURACEQ : FBB). All other care corresponds to routine care. Florbetaben is used during pet scans to visualize beta amyloid plaques and cannot be a separate intervention in and of itself.<br>Device: MRI scan<br>* Subjects will have an MRI scan at inclusion.<br>Biological: APO E genotyping<br>* Subjects will have APO (apolipoprotein) E genotyping if not already known.<br>|
| Other: Alzheimer's without ACA<br>This group is composed of Alzheimer's type dementia without MRI signs in favor of amyloid cerebral angiopathy (ACA). Intervention: Pet scan with FBB Intervention: MRI scan Intervention: APO E genotyping | Device: Pet scan with FBB<br>* Patients will have a pet scan with Florbetaben (NEURACEQ : FBB). All other care corresponds to routine care. Florbetaben is used during pet scans to visualize beta amyloid plaques and cannot be a separate intervention in and of itself.<br>Device: MRI scan<br>* Subjects will have an MRI scan at inclusion.<br>Biological: APO E genotyping<br>* Subjects will have APO (apolipoprotein) E genotyping if not already known.<br>|
| Other: Healthy volunteers<br>This group is composed of healthy volunteers. Intervention: Pet scan with FBB Intervention: MRI scan Intervention: APO E genotyping | Device: Pet scan with FBB<br>* Patients will have a pet scan with Florbetaben (NEURACEQ : FBB). All other care corresponds to routine care. Florbetaben is used during pet scans to visualize beta amyloid plaques and cannot be a separate intervention in and of itself.<br>Device: MRI scan<br>* Subjects will have an MRI scan at inclusion.<br>Biological: APO E genotyping<br>* Subjects will have APO (apolipoprotein) E genotyping if not already known.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PET scan with Florbetaben: Standardized Uptake Value Ratio |  | Day 0 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| On the reference MRI: the number of lobar hemorrhages |  | Day 0 | 
| On the reference MRI: the locations of lobar hemorrhages | Location is defined as choices from among the following: frontal-right; frontal-left; parietal-right; parietal-left; occipital-right; occipital-left; temporal-right; temporal-left. | Day 0 | 
| On the reference MRI: The presence/absence classification for superficial siderosis | The classification corresponds to one of the following: absence; focal (involving < 4 sulci); disseminated (involving 4 or more sulci). | Day 0 | 
| On the reference MRI: the locations of superficial siderosis | Location is defined as choices from among the following: frontal-right; frontal-left; parietal-right; parietal-left; occipital-right; occipital-left; temporal-right; temporal-left. | Day 0 | 
| On the reference MRI: the absolute quantitative count of microbleeds |  | Day 0 | 
| On the reference MRI: microbleed count category | The microbleed count category corresponds to one of the following: 0, 1, 2-4, >4. | Day 0 | 
| On the reference MRI: The predominant location of microbleeds |  | Day 0 | 
| On the reference MRI: a measure of leukoencephalopathy using the ARWMC scale | The age-related white matter changes (ARWMC) rating scale rating only the supratentorial white matter for each frontal, parieto-occipital, and temporal localisation: 0 for no lesions, 1 for focal lesions, 2 for beginning confluence of lesions, and 3 for diffuse involvement of the entire region | Day 0 | 
| Apolipoprotein E genotype | Everyone has two copies of the gene so the resulting combination determines your APOE genotype as one of the following: E2/E2, E2/E3, E2/E4, E3/E3, E3/E4, or E4/E4. | Day 0 |