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Florbetaben as an Amyloid Plaque Marker in Elderly Patients With Focal or Disseminated Superficial Hemosiderosis (FBB ACC)

Primary Purpose

Amyloid Cerebral Angiopathy, Alzheimer Disease

Status
Withdrawn
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Pet scan with FBB
MRI scan
APO E genotyping
Sponsored by
Centre Hospitalier Universitaire de Nīmes
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Amyloid Cerebral Angiopathy

Eligibility Criteria

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

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.

Sites / Locations

  • CHRU de Nîmes - Hôpital Universitaire Carémeau
  • CH de Perpignan - Hôpital Saint Jean

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Other

Other

Other

Other

Arm Label

ACA with isolated hemosiderosis

ACA with lobar hematoma(s)

Alzheimer's without ACA

Healthy volunteers

Arm Description

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

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

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

This group is composed of healthy volunteers. Intervention: Pet scan with FBB Intervention: MRI scan Intervention: APO E genotyping

Outcomes

Primary Outcome Measures

PET scan with Florbetaben: Standardized Uptake Value Ratio

Secondary Outcome Measures

On the reference MRI: the number of lobar hemorrhages
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.
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).
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.
On the reference MRI: the absolute quantitative count of microbleeds
On the reference MRI: microbleed count category
The microbleed count category corresponds to one of the following: 0, 1, 2-4, >4.
On the reference MRI: The predominant location of microbleeds
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
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.

Full Information

First Posted
January 19, 2016
Last Updated
January 21, 2021
Sponsor
Centre Hospitalier Universitaire de Nīmes
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1. Study Identification

Unique Protocol Identification Number
NCT02664571
Brief Title
Florbetaben as an Amyloid Plaque Marker in Elderly Patients With Focal or Disseminated Superficial Hemosiderosis
Acronym
FBB ACC
Official Title
Evaluation of Florbetaben as an Amyloid Plaque Marker in Elderly Patients With Focal or Disseminated Superficial Hemosiderosis
Study Type
Interventional

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Withdrawn
Why Stopped
experimental drug prohibited by the ANSM (French competent authority)
Study Start Date
July 2020 (Anticipated)
Primary Completion Date
July 2021 (Anticipated)
Study Completion Date
July 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Hospitalier Universitaire de Nīmes

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Amyloid Cerebral Angiopathy, Alzheimer Disease

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
InvestigatorOutcomes Assessor
Allocation
Non-Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ACA with isolated hemosiderosis
Arm Type
Other
Arm Description
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
Arm Title
ACA with lobar hematoma(s)
Arm Type
Other
Arm Description
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
Arm Title
Alzheimer's without ACA
Arm Type
Other
Arm Description
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
Arm Title
Healthy volunteers
Arm Type
Other
Arm Description
This group is composed of healthy volunteers. Intervention: Pet scan with FBB Intervention: MRI scan Intervention: APO E genotyping
Intervention Type
Device
Intervention Name(s)
Pet scan with FBB
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
MRI scan
Intervention Description
Subjects will have an MRI scan at inclusion.
Intervention Type
Biological
Intervention Name(s)
APO E genotyping
Intervention Description
Subjects will have APO (apolipoprotein) E genotyping if not already known.
Primary Outcome Measure Information:
Title
PET scan with Florbetaben: Standardized Uptake Value Ratio
Time Frame
Day 0
Secondary Outcome Measure Information:
Title
On the reference MRI: the number of lobar hemorrhages
Time Frame
Day 0
Title
On the reference MRI: the locations of lobar hemorrhages
Description
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.
Time Frame
Day 0
Title
On the reference MRI: The presence/absence classification for superficial siderosis
Description
The classification corresponds to one of the following: absence; focal (involving < 4 sulci); disseminated (involving 4 or more sulci).
Time Frame
Day 0
Title
On the reference MRI: the locations of superficial siderosis
Description
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.
Time Frame
Day 0
Title
On the reference MRI: the absolute quantitative count of microbleeds
Time Frame
Day 0
Title
On the reference MRI: microbleed count category
Description
The microbleed count category corresponds to one of the following: 0, 1, 2-4, >4.
Time Frame
Day 0
Title
On the reference MRI: The predominant location of microbleeds
Time Frame
Day 0
Title
On the reference MRI: a measure of leukoencephalopathy using the ARWMC scale
Description
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
Time Frame
Day 0
Title
Apolipoprotein E genotype
Description
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.
Time Frame
Day 0

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dimitri Renard, MD
Organizational Affiliation
Centre Hospitalier Universitaire de Nîmes
Official's Role
Study Director
Facility Information:
Facility Name
CHRU de Nîmes - Hôpital Universitaire Carémeau
City
Nîmes Cedex 09
ZIP/Postal Code
30029
Country
France
Facility Name
CH de Perpignan - Hôpital Saint Jean
City
Perpignan
ZIP/Postal Code
66046
Country
France

12. IPD Sharing Statement

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

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