Clinical trial NCT02164643: Longitudinal Study of Brain Amyloid imaGing in MEMENTO
Official title: Longitudinal Study of Brain Amyloid imaGing in MEMENTO
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Alzheimer's Disease (AD) and Related Disorders
Keywords: Alzheimer's disease
Mild Cognitive Impairment
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
Collaborators: name: Fondation Plan Alzheimer
name: GE Healthcare
name: Avid Radiopharmaceuticals
First posted: 2014-06-16
Enrollment: 448
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: A Multicenter national longitudinal cohort study including at least 800 individuals consecutively recruited from French Research Memory Centers and followed-up over 24 month and included in Memento.

Detailed description: Alzheimer's disease (AD) is the most common cause of dementia in the elderly, affecting approximately 7.3 million people in Europe. AD is a clinicopathologic entity for which the definitive diagnosis requires both the presence of the clinical signs of dementia and pathological evidence of amyloid plaque in the brain (obtained at autopsy).

Currently, diagnosis of AD at early stage of the disease is hampered by the lack of noninvasive and validated biomarkers of the underlying pathology. On one hand, it is suggested that between 10% and 20% of patients currently diagnosed with AD, based on clinical evidence solely, lack AD pathology at autopsy, and on the other hand community physicians may not diagnose AD in 33% of patients with mild signs and symptoms. Thus, there is a need for validated diagnostic biomarker that could help clinicians separate patients who do not have AD from those who have pathological signs and should be referred for further evaluation and care management. Furthermore, little is known on the prognosis value for dementia conversion of current biomarkers of AD pathology at a preclinical or presymptomatic stage.

Recently, 18F-labeled positron emission tomography (PET) imaging agents have been developed that bind with high affinity to the amyloid-β (Aβ) peptide fibrils that constitute amyloid plaques, and thus, have potential value as an imaging biomarkers for amyloid deposits in subjects with cognitive impairment or isolated cognitive complaints.

The principal objective of this ancillary study is to investigate the prospective association between PET amyloid load, measured twice two years apart, through either Florbetapir (18F) or Flutemetamol (18F) radioligands, and dementia incidence over up to 5 years of follow-up in a sample of individuals presenting with a spectrum of cognitive profiles ranging from isolated cognitive complaints to cognitive deficits without dementia.

The secondary objectives are the following:

* To assess the association between change in amyloid load and clinical evolution of participants (both functional and cognitive)
* To estimate the prevalence of new research criteria for preclinical Alzheimer's disease
* To investigate long-term outcome of preclinical Alzheimer's disease according to NIA-AA criteria
* To assess the determinants of change in amyloid load over two years
* To study the interrelationships between biomarkers
* To assess the added value of amyloid binding agent (Florbetapir (18F) and Flutemetamol (18F)) in combination with other biomarkers (neuropsychological, genetics, plasma, serum, CSF, structural neuroimaging, 18F-FDG-PET) to predict clinical dementia onset
* To assess the diagnostic accuracy of amyloid agent Florbetapir (18F) and Flutemetamol (18F) to differentiate AD from other types of dementia (differential diagnosis)
* To study the link between amyloid binding agent and survivalstudy design

Eligibility criteria: Inclusion Criteria:

* To be included in MEMENTO
* To have signed a specific MEMENTO-AmyGing informed consent form, prior to any amyloid PET procedures
* To have had or agreed to have 18F-FDG PET scan in MEMENTO
* To tolerate the (18F) PET scan procedures, in the opinion of the clinical site investigator
* Clinical Dementia Rating scale \<0.5 and not demented

Exclusion Criteria:

* To have a current clinically significant psychiatric condition that neurologists/geriatricians feel would preclude the ability to have a research PET scan
* To be pregnant or breastfeading women
* To have Hypersensitivity to the tracer or to the excipient listed in the summary of the product carateristics (florbetapir Amyvid®) or the Investigator's Brochure (flutemetamol)
* To have a relevant history of severe drug allergy or hypersensitivity (relevant severe drug allergies should be determined by the clinical site investigator or co-clinical site investigator). If a subject has a history of severe drug allergies, it may be dangerous for them to participate in a study with a novel compound
* To have ever participated in an experimental study with an amyloid targeting agent (e.g. anti-amyloid immunotherapy, γ-secretase or γ-secretase inhibitor) unless it can be documented that the subject received only placebo during the course of the trial
* To receive any investigational medications, or have participated in a trial with investigational medications within the last 30 days
* To have participated less than 1 year ago in a biomedical research with injection of one of the amyloid radioligand or to be enrolled in an ongoing biomedical research including amyloid PET scan
* To have had a radiopharmaceutical imaging or treatment procedure within 7 days prior to the study imaging session

Primary outcomes:
measure: Progression to clinical dementia stage according to standardized classifications (DSM-IV and NINCDS-ADRDA) as described in the MEMENTO protocol.
timeFrame: 24 months from baseline
Secondary outcomes:
measure: Longitudinal evolution of amyloid load measured through either Florbetapir (18F) or Flutemetamol (18F)
timeFrame: 24 months from baseline
measure: Speed of cognitive decline based on change in cognitive performances
timeFrame: 24 months from baseline
measure: Longitudinal evolution of biomarkers measured from blood, CSF, structural neuroimaging (MRI) and glucose metabolism molecular neuroimaging (18F-FDG PET).
timeFrame: 24 months from baseline
measure: Mortality
timeFrame: 24 months from baseline
measure: Loss of autonomy based on functional activity assessment
timeFrame: 24 months from baseline
measure: Institutionalization
timeFrame: 24 months from baseline
measure: Cardiovascular event (Stroke and Coronary events)
timeFrame: 24 months from baseline
measure: Quality of life
timeFrame: 24 months from baseline
measure: Prodromal AD (Pre-symptomatic dementia)
timeFrame: 24 months from the baseline
measure: Etiology of dementia, when converted
timeFrame: 24 months from the baseline
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU d'Angers
city: Besancon
country: France
facility: CHU de Besançon
city: Bobigny
country: France
facility: AP-HP - Avicenne
city: Bordeaux
country: France
facility: CHU de Bordeaux - Pellegrin
city: Bordeaux
country: France
facility: CHU de Bordeaux - Hôpital Xavier-Arnozan
city: Brest
country: France
facility: CHU de Brest
city: Clermont-ferrand
country: France
facility: CHU de Clermont-Ferrand
city: Dijon
country: France
facility: CHU de Dijon
city: Grenoble
country: France
facility: CHU de Grenoble
city: Lille
country: France
facility: CHU de Lille
city: Lyon
country: France
facility: Hospices civils de Lyon
city: Marseille
country: France
facility: AP-HM
city: Montpellier
country: France
facility: CHU de Montpellier
city: Nancy
country: France
facility: CHU de Nancy
city: Nice
country: France
facility: CHU de Nice
city: Paris
country: France
facility: AP-HP - Hôpital BROCA
city: Paris
country: France
facility: AP-HP - Hôpital LARIBOISIERE
city: Paris
country: France
facility: Ap-Hp La Pitié-Salpêtrière
city: Poitiers
country: France
facility: CHU de Poitiers
city: Rouen
country: France
facility: CHU de Rouen
city: Saint-etienne
country: France
facility: CHU de Saint-Etienne - Hôpital de la charité
city: Saint-etienne
country: France
facility: CHU de Saint-Etienne - Hôpital Nord
city: Strasbourg
country: France
facility: CHU de Strasbourg
city: Toulouse
country: France
facility: CHU de Toulouse - Hôpital Purpan
city: Toulouse
country: France
facility: CHU de Toulouse
city: Tours
country: France
facility: CHU de Tours
Study officials:
affiliation: CIC-EC7 - ISPED - CHU de Bodeaux
name: Genevieve CHENE, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: CIC-EC7 - ISPED - CHU de Bordeaux
name: Geneviève CHENE, Prof
role: STUDY_CHAIR
affiliation: CIC-EC7 - ISPED - CHU de Bordeaux
name: Carole DUFOUIL, Director
role: STUDY_DIRECTOR
affiliation: Head of Lille Memory Clinic, CHRU Lille
name: Florence PASQUIER, Prof
role: STUDY_DIRECTOR
affiliation: Head of Molecular Imaging Work package for the Center for Image Acquisition and Processing - CHU Pitié-Salpêtrière, AP-HP
name: Marie-Odile HABERT, Prof
role: STUDY_DIRECTOR
References: