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

• ClinicalTrials.gov Identifier: NCT02664571
• Recruitment Status: Not yet recruiting
• First Posted: January 27, 2016
• Last Update Posted: January 14, 2019
• Sponsor: Centre Hospitalier Universitaire de Nīmes
• Information provided by (Responsible Party): Centre Hospitalier Universitaire de Nīmes

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.

Condition or disease	Intervention/treatment	Phase
Amyloid Cerebral Angiopathy; Alzheimer Disease	Device: Pet scan with FBB; Device: MRI scan; Biological: APO E genotyping	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 32 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Investigator, Outcomes Assessor)
• Primary Purpose: Diagnostic
• Official Title: Evaluation of Florbetaben as an Amyloid Plaque Marker in Elderly Patients With Focal or Disseminated Superficial Hemosiderosis
• Estimated Study Start Date: January 2020
• Estimated Primary Completion Date: January 2021
• Estimated Study Completion Date: January 2021

Arms and Interventions

Arm	Intervention/treatment
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.
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.
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.
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.

Outcome Measures

Primary Outcome Measures :

1. PET scan with Florbetaben: Standardized Uptake Value Ratio [ Time Frame: Day 0 ]

Secondary Outcome Measures :

1. On the reference MRI: the number of lobar hemorrhages [ Time Frame: Day 0 ]
2. On the reference MRI: the locations of lobar hemorrhages [ Time Frame: Day 0 ]
   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.
3. On the reference MRI: The presence/absence classification for superficial siderosis [ Time Frame: Day 0 ]
   The classification corresponds to one of the following: absence; focal (involving < 4 sulci); disseminated (involving 4 or more sulci).
4. On the reference MRI: the locations of superficial siderosis [ Time Frame: Day 0 ]
   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.
5. On the reference MRI: the absolute quantitative count of microbleeds [ Time Frame: Day 0 ]
6. On the reference MRI: microbleed count category [ Time Frame: Day 0 ]
   The microbleed count category corresponds to one of the following: 0, 1, 2-4, >4.
7. On the reference MRI: The predominant location of microbleeds [ Time Frame: Day 0 ]
8. On the reference MRI: a measure of leukoencephalopathy using the ARWMC scale [ Time Frame: Day 0 ]
   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
9. Apolipoprotein E genotype [ Time Frame: Day 0 ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 60 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Contacts

Contact: Dimitri Renard, MD; +33(.0)4.66.68.38.35; dimitrirenaud@hotmail.com

Contact: Carey Suehs, PhD; +33.(0)4.66.68.67.88; carey.suehs@chu-nimes.fr

Locations

France

CHRU de Nîmes - Hôpital Universitaire Carémeau; Not yet recruiting

Nîmes Cedex 09, France, 30029

Principal Investigator: Dimitri Renard, MD

Sub-Investigator: Laurent Collombier, MD

Sub-Investigator: Benjamin Chambert, MD

CH de Perpignan - Hôpital Saint Jean; Not yet recruiting

Perpignan, France, 66046

Principal Investigator: Denis Sablot, MD

Sponsors and Collaborators

Centre Hospitalier Universitaire de Nīmes

Investigators

• Study Director: Dimitri Renard, MD; Centre Hospitalier Universitaire de Nîmes

More Information

• Responsible Party: Centre Hospitalier Universitaire de Nīmes
• ClinicalTrials.gov Identifier: NCT02664571 History of Changes
• Other Study ID Numbers: LOCAL/2015/DM-01; 2015-004583-11 ( EudraCT Number )
• First Posted: January 27, 2016
• Last Update Posted: January 14, 2019
• Last Verified: January 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Alzheimer Disease; Amyloidosis; Hemosiderosis; Plaque, Amyloid; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Proteostasis Deficiencies; Metabolic Diseases; Iron Overload; Iron Metabolism Disorders; Pathological Conditions, Anatomical