Validation of Blood Biomarkers for Alzheimer's Disease

Last updated: May 2, 2024
Sponsor: University Hospital, Montpellier
Overall Status: Active - Recruiting

Phase

N/A

Condition

Dementia

Mild Cognitive Impairment

Memory Loss

Treatment

Measurement of amyloid and pTau blood biomarkers

Clinical Study ID

NCT05427448
21_0586
  • Ages > 18
  • All Genders

Study Summary

Alzheimer's disease (AD) has gradually become one of the major global public health issues due to its prevalence, which increases with age and life expectancy, and the economic cost of caring for patients whose cognitive decline progressively leads to loss of functional autonomy.

The diagnosis of AD is based on a multidisciplinary approach, involving, among other things, evaluation of the medical history together with clinical symptoms and signs, neuropsychological tests and neuroimaging. The quantification of cerebrospinal fluid (CSF) core biomarkers (amyloid beta peptides [Ab1-40 and Ab1-42], total tau [t-tau] and its phosphorylated form on threonine 181 [p-tau(181)]) has progressively proven utility for the diagnosis of AD and its prodromal forms. CSF biomarkers are now included in international guidelines for the diagnosis of AD in research settings and clinical practice and the Alzheimer's Association appropriate use criteria for the use of lumbar puncture and CSF testing in the diagnosis of AD have been published. Such biochemical diagnostics are currently implemented in many specialized centers around the world.

Recent progress in the biological diagnosis of AD is considerable, with the possibility, thanks to ultra-sensitive tests realized notably with the SIMOA technology, of having Ab1-40, Ab1-42, t-tau and p-tau(181) also detectable in the blood using commercial kits. The performance for AD detection has been evaluated by many groups including on retrospective samples.

It is now essential to evaluate the interest of blood-based biomarkers of AD, prospectively and in real life condition to confront them with pre-analytical and analytical variabilities. It is also important to position them in relation to CSF analysis and AD management, from risk assessment, diagnosis, to therapeutic strategies.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Patients consulting in memory clinics from Montpellier, Nîmes, or Perpignan.
  • Age >= 18 years old
  • CSF AD biomarkers performed for diagnostic purpose in clinical routine practice
  • Having given their written and enlightened consent
  • Affiliated or beneficiary of the national health insurance

Exclusion

Exclusion Criteria:

  • Contraindication or refusal of lumbar puncture
  • Patient deprived of freedom, by court or administrative order, or major protected bylaw
  • Pregnant or breastfeeding women

Study Design

Total Participants: 342
Treatment Group(s): 1
Primary Treatment: Measurement of amyloid and pTau blood biomarkers
Phase:
Study Start date:
November 24, 2022
Estimated Completion Date:
December 31, 2024

Study Description

Rationale of the project:

Recent progress in the biological diagnosis of Alzheimer's disease (AD) is considerable, with the possibility, thanks in particular to ultra-sensitive tests, of having relevant blood biomarkers. These biomarkers, mainly represented by amyloid peptides, tau proteins and neurofilaments, make it possible to consider a stratification of patients according to different classifications, including the ATN scale. Their diagnostic value has been mainly tested on retrospective samples and it is now essential to use them prospectively to confront them with pre-analytical and analytical variability. It is also important to position them in relation to CSF analysis and AD management, from risk assessment, diagnosis, to therapeutic strategies.

Main objective:

To evaluate, in a prospective consecutive enrollment clinical trial, the diagnostic performance (sensitivity, specificity) of blood biomarkers for Alzheimer's disease.

Secondary objectives:

  • Interest of blood biomarkers for detection of normal/pathological CSF profiles.

  • Interest of blood biomarkers for other disease including, amyloid angiopathy, frontotemporal dementia (FTD) or lewy body disease (LBD).

Methodology:

The investigator's laboratory daily receives CSF samples from regional "memory clinics" (mainly from Montpellier, Nîmes, Perpignan) for Aß40, Aß42, t-Tau and p-Tau(181) assays. The results of these tests performed weekly on an automated platform are used by neurologists for the diagnosis of AD. In this non-interventional multi-center clinical trial, with the informed consent of patients, one tube of plasma in addition to CSF is collected. In parallel with the CSF, amyloid peptides and plasma p-Tau is measured. The ApoE4 status will also be determined using MS as previously published by the investigator's group. Plasma biomarkers will then be combined to confirm the presence of AD, as has already been done on retrospective samples by the investigator's laboratory and others. Considering a disease prevalence rate of 20% in the screened population, and to reach a sensitivity of 80% and a specificity close to 90%, it is necessary to include a total of 311 patients in order to obtain an estimate of sensitivity and specificity with a 95% accuracy of +/- 10%. The lost to follow-up rate of about 10% requires the enrollment of 342 patients. The diagnostic performance of this profile will be compared to that of CSF, as well as to the diagnosis assessed by a multidisciplinary team one year after sampling.

Expected benefit:

The confirmation that blood biomarkers of AD achieve satisfactory diagnostic performance in a clinical setting allows them to be considered in routine use, as a less invasive method, thus with greater acceptance and also the possibility of longitudinal use. The benefit also lies in the evaluation of the interest of supplemental biomarkers such as NfL, for related diseases.

Connect with a study center

  • Montpellier University Hospital

    Montpellier, Occitanie 34000
    France

    Active - Recruiting

  • Nîmes University Hospital

    Nîmes, Occitanie 30000
    France

    Active - Recruiting

  • Perpignan Regional Hospital

    Perpignan, Occitanie 66000
    France

    Active - Recruiting

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