New Biomarker for Alzheimer's Disease Diagnostic (BALTAZAR)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01315639
First received: March 11, 2011
Last updated: July 25, 2014
Last verified: July 2014
  Purpose

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.

Condition Intervention
Alzheimer's Disease
Mild Cognitive Impairment
Biological: biomarkers, MRI and CSF

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
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

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Mean concentration of plasma AB peptides [ Time Frame: at t0 and 24 months ] [ Designated as safety issue: No ]
    • MCI "converted" (MCI-AD)
    • and stable MCI (MCI-MCI) groups


Secondary Outcome Measures:
  • Mean concentration of biomarker [ Time Frame: t0 and 24 months ] [ Designated as safety issue: No ]
    • Mean plasma concentration of AB peptides between

      • fast decliner AD (decline of 7 points or more in ADAS-cog)
      • and non fast decliner AD groups
    • Mean concentration of sAPPalpha between

      • MCI "converted" (MCI-AD)
      • and stable MCI (MCI-MCI) groups
    • Mean concentration of sAPPalpha between

      • fast decliner AD (decline of 7 points or more in ADAS-cog)
      • and non fast decliner AD groups

  • MRI [ Time Frame: T0 + M24 or conversion ] [ Designated as safety issue: No ]
    •Relationship between MRI measures (brain volume, hippocampus atrophy, vascular lesions) and biomarkers

  • Transcriptomics biomarkers [ Time Frame: T0 and 24 months or conversions ] [ Designated as safety issue: No ]
    • Relationship between transcriptomics biomarkers and cognitive decline


Estimated Enrollment: 1300
Study Start Date: August 2010
Estimated Study Completion Date: February 2019
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
biomarkers, MRI and CSF

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).

Biological: 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

Detailed 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.

  Eligibility

Ages Eligible for Study:   45 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01315639

Contacts
Contact: Olivier Hanon, MD, PhD 0033144083502 olivier.hanon@brc.aphp.fr
Contact: Laurence LECOMTE, PhD 0033158413545 laurence.lecomte@cch.aphp.fr

Locations
France
APHP, Hôpital Broca Recruiting
Paris, France, 75013
Principal Investigator: Olivier Hanon, MD, PhD         
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Olivier Hanon, ph Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01315639     History of Changes
Other Study ID Numbers: P081205
Study First Received: March 11, 2011
Last Updated: July 25, 2014
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Dementia
Cognitive impairment
Memory impairment
Mild Cognitive Impairment
Cerebrospinal fluid
Plasma
Biomarker
Longitudinal
Abeta peptide amyloid, saPP alpha
Oculomotor impairment

Additional relevant MeSH terms:
Alzheimer Disease
Cognition Disorders
Mild Cognitive Impairment
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on September 18, 2014