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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Alzheimer Disease; Amyloid Cerebral Angiopathy
• Intervention / Treatment: Device: Pet scan with FBB; Device: MRI scan; Biological: APO E genotyping

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.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Nîmes Cedex 09, France, 30029
    • CHRU de Nîmes - Hôpital Universitaire Carémeau
  • Perpignan, France, 66046
    • CH de Perpignan - Hôpital Saint Jean

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: ACA with isolated hemosiderosis; 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; 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.; Device: MRI scan; Subjects will have an MRI scan at inclusion.; Biological: APO E genotyping; Subjects will have APO (apolipoprotein) E genotyping if not already known.
Other: ACA with lobar hematoma(s); 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; 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.; Device: MRI scan; Subjects will have an MRI scan at inclusion.; Biological: APO E genotyping; Subjects will have APO (apolipoprotein) E genotyping if not already known.
Other: Alzheimer's without ACA; 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; 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.; Device: MRI scan; Subjects will have an MRI scan at inclusion.; Biological: APO E genotyping; Subjects will have APO (apolipoprotein) E genotyping if not already known.
Other: Healthy volunteers; This group is composed of healthy volunteers. Intervention: Pet scan with FBB Intervention: MRI scan Intervention: APO E genotyping	Device: Pet scan with FBB; 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.; Device: MRI scan; Subjects will have an MRI scan at inclusion.; Biological: APO E genotyping; Subjects will have APO (apolipoprotein) E genotyping if not already known.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nīmes
• Investigators: Study Director: Dimitri Renard, MD, Centre Hospitalier Universitaire de Nîmes

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2020
• Primary Completion (Anticipated): July 1, 2021
• Study Completion (Anticipated): July 1, 2021

Study Registration Dates

• First Submitted: January 19, 2016
• First Submitted That Met QC Criteria: January 22, 2016
• First Posted (Estimate): January 27, 2016

Study Record Updates

• Last Update Posted (Actual): January 25, 2021
• Last Update Submitted That Met QC Criteria: January 21, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Genetic Diseases, Inborn; Neurodegenerative Diseases; Pathological Conditions, Anatomical; Iron Metabolism Disorders; Proteostasis Deficiencies; Metabolism, Inborn Errors; Dementia; Tauopathies; Metal Metabolism, Inborn Errors; Iron Overload; Amyloidosis; Alzheimer Disease; Hemochromatosis; Hemosiderosis; Plaque, Amyloid
• Other Study ID Numbers: LOCAL/2015/DM-01; 2015-004583-11 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No