ADDIA Proof-of-Performance Clinical Study

NCT03030586 | Completed

• 1 other identifier: ST0056
• Study Type: observational
• Target: 821
• Locations: 5 countries
• Sites: 13

Brief Summary

The objective of the ADDIA clinical Proof-of-Performance study is to validate the performance of ADDIA' blood biomarkers for diagnosis of Alzheimer's disease (AD). ADDIA clinical study is a multi-centre, non-interventional, prospective, proof-of-performance study with only one visit. About 800 well-characterized subjects will be recruited into 3 groups in 2:1:1 ratio, namely patients with Alzheimer's disease (AD), patients with non-AD neurodegenerative disease (NAD) and 200 control subjects (healthy as compared to their age).

• 400 patients with Alzheimer's disease (AD): 200 patients with mild AD, 200 patients with moderate-to-severe AD,
• 200 patients with non-Alzheimer's neurodegenerative diseases (NAD),
• 200 controls (healthy as compared to their age).

Conditions

Alzheimer Disease (AD); Frontotemporal Lobar Degeneration; Dementia with Lewy Bodies (DLB); Parkinson Disease Dementia (PDD); Progressive Supranuclear Palsy (PSP); Corticobasal Degeneration (CBD)

Keywords

Blood cell biomarkers, peripheral circulating biomarkers

Outcome Measures

Primary Outcomes (1)

• Blood cell biomarkers for diagnosis of Alzheimer

  Proof of Performance of ADDIA' blood biomarker-based test

  18 Months

Secondary Outcomes (1)

• Biomarkers circulating in body fluids for diagnosis of Alzheimer and/or other dementia type

  18 months

Study Arms (3)

Alzheimer

400 patients in total, with approximately 200 patients with mild Alzheimer's disease and 200 patients with moderate to severe Alzheimer's disease will be recruited for sampling blood, urine (and other peripheral body fluids: tears and saliva as optional) for validation of biomarkers

Other: volumetric MRI

Non-Alzheimer neurodegenerative disease

200 patients comprising: * 75 patients with behavioural variant of Fronto-Temporal Lobe Degeneration (FTD), * 50 patients with Parkinson's disease dementia (PDD), * 50 patients with Dementia with Lewy Bodies (DLB) and * 25 patients with Progressive Supranuclear Palsy (PSP) or cortico-basal degeneration (CBD)

Other: volumetric MRI

Healthy Controls

200 healthy subjects

Other: volumetric MRI

Interventions

volumetric MRI OTHER

Alzheimer; Healthy Controls; Non-Alzheimer neurodegenerative disease

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

About 800 well characterized subjects will be enrolled into 3 groups in 2:1:1 ratio, namely patients with Alzheimer's disease (AD), patients with non-AD neurodegenerative disease (NAD) and control subjects (healthy as compared to their age). The number of subjects is divided into 3 groups as following: * 400 patients with AD (50% with mild AD and 50% of with moderate to severe AD), * 200 patients with non-Alzheimer's neurodegenerative diseases (NAD): this group will comprise 75 patients with behavioural variant of Fronto-Temporal Lobe Degeneration (FTD) recruited according to Rascovsky et al., 2011; 50 patients with Parkinson's disease dementia (PDD), 50 patients with Lewy Body dementia (DLB) recruited according to McKeith et al., 2005 criteria; 25 patients with Progressive Supranuclear Palsy (PSP) or cortico-basal degeneration (CBD). * 200 controls (healthy as compared to their age).

You may qualify if:

• For all groups:
• Female and male subjects aged 40 to 85 years.
• Dated and signed informed consent by the subject (or its legal representative if applicable in accordance with the local regulations).
• AD, NAD patients and control subjects will be age-matched and mean age similar in the three groups.
• Able to comply with all study procedures.
• For AD group:
• Diagnosis of AD: typical and atypical AD.
• MMSE score (measured in the last 3 months): \< 21 for patients with moderate to severe AD. MMSE score \> 21 in subjects with mild AD with sporadic or a familial form of AD due to mutation in APP or PSEN1 or PSEN2 genes.
• FCSRT, MoCA tests (MoCA measured in the last 3 months).
• Neuroimaging compatible with a diagnosis of AD:
• At least quantitative volumetric structural MRI: volumes of hippocampus and cortical areas.
• Visual semi-quantitative MRI if practiced shall show medial temporal lobe atrophy (MTA) and parietal atrophy with visual rating (semi-quantitative) on the MTA-score (e.g. Scheltens' scores 0-4). MTA score must be ≥ 2 in patients aged 40-75 years and ≥ 3 in patients aged above 75 years. For patients younger than 60 years, and with familial form of AD, who may have normal MTA-scores, Koedam score (0-3) for Parietal Atrophy showing atrophy of the precuneus characteristic of AD may be used with a Koedam score from 1 to 3.
• Other neuroimaging data (retrospectively available) including PET Amyloid scan and FDG PET are desired if practiced by clinical centres and if available.
• \- Cerebrospinal fluid biomarker data (retrospectively available) showing positive levels of at least 2 out of 3 biomarkers: i.e. Aβ1-42 and tau (phosphorylated-Tau and/or total-Tau). Note: If retrospective CSF data are not available, retrospective Aβ PET and Tau PET data can be used.
• For NAD group:

You may not qualify if:

• Brain MRI at Screening consistent with PSP: neuroradiologic evidence of relevant structural abnormality in the midbrain and frontal lobes (i.e. basal ganglia, lobar atrophy).
• MMSE score compatible.
• Be able to ambulate and stand unassisted for 5 minutes.
• Be able to cooperate with gait and balance testing.
• Corticobasal degeneration (CBD)
• Features of CBS: a) limb rigidity or akinesia, b) limb dystonia, c) limb myoclonus plus 1 of: d) orobuccal or limb apraxia, e) cortical sensory deficit, f) alien limb phenomena (more than simple levitation).
• Features of PSPS: Three of: a) axial or symmetric limb rigidity or akinesia, b) postural instability or falls, c) urinary incontinence, d) behavioural changes, e) supranuclear vertical gaze palsy or decreased velocity of vertical saccades.
• Note: subjects with probable sporadic CBD (no familial form) are excluded.
• MRI findings: parietal cortical atrophy (asymmetric).
• MMSE score compatible.
• Controls
• Normal cognitive performance with normal scores of neuropsychological tests for their age.
• MMSE \>26 (performed in less than 3 months).
• At least volumetric structural MRI with normal findings. Normal retrospective finding in β-amyloid PET scan, FDG PET scan if practiced by clinical centres.
• If retrospectively available, normal CSF biomarkers concentrations: negative levels for all three CSF biomarkers Aβ1-42, phosphorylated-Tau and total-Tau.

Sponsors & Collaborators

• Amoneta Diagnostics SAS: lead
• European Commission: collaborator
• Firalis SA: collaborator
• University Hospital, Strasbourg: collaborator
• Centre Hospitalier Universitaire Vaudois: collaborator
• IRCCS Centro San Giovanni di Dio Fatebenefratelli: collaborator
• Hopitaux Civils de Colmar: collaborator
• Istanbul University: collaborator
• Assistance Publique - Hôpitaux de Paris: collaborator
• University Hospital, Lille: collaborator
• University Hospital, Geneva: collaborator
• Cliniques universitaires Saint-Luc- Université Catholique de Louvain: collaborator
• Erasme University Hospital: collaborator
• University Hospital, Montpellier: collaborator
• Centre Hospitalier Universitaire de Besancon: collaborator
• Centre Hospitalier Universitaire de Nice: collaborator

Study Sites (13)

Cliniques Universitaires Saint-Luc

Brussels, Belgium

Location

ERASME Hospital

Brussels, Belgium

Location

Hopitaux Universitaires de Strasbourg

Strasbourg, Alsace, France

Location

Centre Hospitalier Universitaire de Besançon

Besançon, France

Location

Hôpitaux Civils (Hopital Louis Pasteur) de Colmar

Colmar, France

Location

Centre Hospitalier Régional Universitaire de Lille

Lille, France

Location

Centre Hospitalier Universitaire de Montpellier

Montpellier, France

Location

Centre Hospitalier Universitaire de Nice

Nice, France

Location

APHP-Hôpitaux Universitaires Pitié Salpêtrière

Paris, France

Location

IRCCS Centro San Giovanni di Dio Fatenenefratelli

Brescia, Brescia, Italy

Location

Hôpitaux Universitaires de Genève

Geneva, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, Switzerland

Location

Istanbul University Hospital

Istanbul, Turkey (Türkiye)

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood

MeSH Terms

Conditions

Alzheimer Disease; Frontotemporal Lobar Degeneration; Lewy Body Disease; Supranuclear Palsy, Progressive; Corticobasal Degeneration

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Ophthalmoplegia; Ocular Motility Disorders; Cranial Nerve Diseases; Paralysis; Neurologic Manifestations; Eye Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Frédéric Blanc, MD

  Hôpitaux Universitaires Strasbourg

  PRINCIPAL INVESTIGATOR

• Jean-François Démonet, MD

  Centre hospitalier universitaire vaudois, Lausanne

  PRINCIPAL INVESTIGATOR

• Hakan Gurvit, MD

  Istanbul University, Istanbul

  PRINCIPAL INVESTIGATOR

• Moira Marizzoni, PhD

  IRCCS Centro San Giovanni di Dio Fatenenefratelli, Bressia

  PRINCIPAL INVESTIGATOR

• François Sellal, MD

  Hôpitaux Civils (Hopital Louis Pasteur) de Colmar

  PRINCIPAL INVESTIGATOR

• Frisoni Giovanni, MD

  University Hospital, Geneva

  PRINCIPAL INVESTIGATOR

• Florence Pasquier, MD

  Centre Hospitalier Régional, Universitaire de Lille

  PRINCIPAL INVESTIGATOR

• Adrian Ivanoiu, MD

  Cliniques Universitaires Saint-Luc, Brussels

  PRINCIPAL INVESTIGATOR

• Bruno Dubois, MD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

• Jean-Christophe Bier, MD

  Hopital ERASME, Brussels

  PRINCIPAL INVESTIGATOR

• Audrey Gabelle, MD

  University Hospital, Montpellier

  PRINCIPAL INVESTIGATOR

• Eloi Magnin, MD

  Centre Hospitalier Universitaire de Besançon

  PRINCIPAL INVESTIGATOR

• Renaud David, MD

  Centre Hospitalier Universitaire de Nice

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2017
• First Posted: January 25, 2017
• Study Start: September 1, 2016
• Primary Completion: June 30, 2023
• Study Completion: June 30, 2023
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (7); BE (2); CH (2); TU (1); IT (1)