Overview

This trial is active, not recruiting.

Conditions alzheimer's disease, mild cognitive impairment
Treatment biomarkers, mri and csf
Sponsor Assistance Publique - Hôpitaux de Paris
Start date August 2010
End date September 2018
Trial size 1067 participants
Trial identifier NCT01315639, P081205

Summary

The aim of this study is to examine the relationship between plasma putative biomarkers for Alzheimer's disease (i.e. Ab40 amyloid and total Ab42 amyloid, free, bound, free/bound, truncated, sAPPα) and :

- the risk of conversion of individuals with Mild Cognitive Impairment (MCI) into Alzheimer's disease (AD),

- the Alzheimer's disease progression rate.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Intervention model single group assignment
Masking open label
Primary purpose diagnostic
Arm
(Other)
Longitudinal multicenter study including 1300 subjects with amnestic impairment (MCI, n=650 and AD, n=650) derived from the main French national Memory Resources and Research Centers. Participants will undergo at baseline and every 6 months a neurological examination, a neuropsychological assessment (and an oculomotor examination for those included from Broca Hospital). Alzheimer disease biomarkers' measurements will be performed at inclusion and at the end of the study (or the conversion).
biomarkers, mri and csf
MRI at Day 0 and month 24 (or conversion) Biomarkers at Day 0 et month 24 (or conversion) CSF at D0

Primary Outcomes

Measure
Mean concentration of plasma AB peptides
time frame: at t0 and 24 months
plasma levels of Tau protein
time frame: t0

Secondary Outcomes

Measure
Mean concentration of biomarker
time frame: t0 and 24 months
MRI
time frame: T0 + M24 or conversion
Transcriptomics biomarkers
time frame: T0 and 24 months or conversions
Bace peptide
time frame: t0
TACE/ADAM17
time frame: to
Cathepsin
time frame: t0
sAPPβ
time frame: t0
Ratio of CSF sAPPβ and CSF sAPPα
time frame: t0
Ratio of plasma Aβ and plasma Tau
time frame: t0
Plasma Tau
time frame: 24 months
MRI biomarkers
time frame: t0
MRI biomarkers
time frame: 24 months

Eligibility Criteria

Male or female participants at least 45 years old.

Inclusion Criteria: MCI group : - ≥ 70 years - MCI diagnosis : New criteria (Petersen, PORTET*) 1. cognitive complaint from the patient, family, or both, 2. report by the subject or reporter of a decline in cognitive or functional performance, relative to previous abilities, 3. cognitive disorders evidenced by clinical evaluation: impairment in memory or another cognitive domain, 4. cognitive impairment without any repercussion on daily life, even if the subject reports difficulties concerning complex daily activities, 5. no dementia - Having signed an informed consent form - Fluent in French AD group : - ≥ 45 years - AD diagnosis (DSM IV-TR et NINCDS-ADRDA) - Mild to moderate (MMSE > 15) - Having signed an informed consent form - Caregiver/informant to provide information on patient Exclusion Criteria: - Normal cognitive function - Major depression (according to the DSMIV-TR or MINI or Geriatric depression Scale> 20/30) - Genetic form of AD (genetic mutation known) - All other diseases that could interfere with cognitive assessment (Epilepsy, Parkinson's disease, schizophrenia, other dementia) - Major sensory deficits that could interfere with cognitive assessment (visual and auditory) - Diseases involving the short-term survival (advanced cancer, unstable heart disease, severe hepatic/respiratory/renal failure) - Contraindication for MRI, for lumbar puncture (i.e. anticoagulant agents) - Use of any experimental agent for the duration of the study - Participation to other biomedical research that could interfere with principal objective of the study - For MCI patient, use of IchE or memantine medication before inclusion - Less than 4 years of education - Illiteracy, is unable to count or to read - Pregnant women - Non health insurance affiliation - Private subjects of freedom by legal or administrative decision - Contraindication for MRI examination: - Claustrophobic subject - Carrying a cardiac pacemaker - Presence of any ferromagnetic metallic implants or foreign bodies (carrying an internal electrical/magnetic device, carrying a valvular prosthesis) - Carrying a ventricular valvular Exclusion criteria specific to the lumbar puncture: • Taking anticoagulant agents

Additional Information

Official title Plasma Abeta Peptides and the Risk of Alzheimer's Disease. Diagnostic Performance and Predictive and Prognostic Values of Measurements of Plasma Amyloid Peptides Concentrations for the Diagnosis of Alzheimer's Disease
Principal investigator Olivier Hanon, ph
Description Rational Whether there are biological markers of Alzheimer's disease (AD) is crucial for adequate targeting and appropriate management of the disease. The aim of our study is to examine diagnostic performance and predictive and prognostic values of new plasma markers of AD. Results of studies on the predictive value of plasma concentrations of Aβ40 and 42 amyloid peptides for incident AD are not straightforward. Discrepancies in these results may be due to the fact that total peptide concentrations have been measured. One recent study suggests that plasma free Aβ peptide concentration and particularly low-density lipoprotein receptor-related protein (LPR) as like as free Aβ/total Aβ ratio would be more reliable and discriminant. Main objective of the study To examine the association between plasma free Aβ peptide concentration and (1) the risk of conversion of subjects with Mild Cognitive Impairment (MCI) into Alzheimer's disease (AD) and (2) the risk of worsening of the disease in patients with mild and moderate stages of AD. Secondary objectives - To examine the association of total peptid Aβ concentration, free Aβ/Total Aβ ratio, and trunked plasmatic Aβ to the risk of incident AD in MCI subjects, and to the risk of worsening of the disease in mild and moderate AD patients, - To examine the association between serum sAPP concentration and the risk of incident AD in MCI subjects, and the risk of worsening of the disease in mild and moderate AD patients, - To compare the time evolution of concentrations of these biomarkers to Alzheimer's disease progression rate which will be assessed on the basis of neuropsychological examinations and MRI examination of hippocampal atrophy, - To examine the association between serum and cerebrospinal fluid (CSF) concentrations of AD biomarkers in subgroup of participants who undergo lumbar puncture, - To examine the association between neuroimaging data (cerebral volume, hippocampal volume, cerebrovascular lesions and plasma and CSF AD biomarkers' concentrations, - To constitute blood and plasma banks, gene bank and CSF bank for future studies on other biomarkers of AD. Design and Methods Longitudinal multicenter study including 1300 subjects with amnestic impairment (MCI, n=650 and AD, n=650) derived from the main French national Memory Resources and Research Centers. Participants will undergo at baseline and every 6 months a neurological examination, a neuropsychological assessment (and an oculomotor examination for those included from Broca Hospital). Alzheimer disease biomarkers' measurements will be performed at inclusion and at the end of the study. For those MCI participants who convert to dementia, the end of the study will correspond to the AD conversion period. A Magnetic Resonance Imaging (MRI) scan will be performed at inclusion and at the end of the study for MCI subjects who convert into AD. A lumbar puncture on an outpatient basis will be performed at study entry in all participants who will give an informed consent for this examination in absence of contraindication.
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by Assistance Publique - Hôpitaux de Paris.