Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

ADDIA Proof-of-Performance Clinical Study (ADDIA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03030586
Recruitment Status : Recruiting
First Posted : January 25, 2017
Last Update Posted : December 5, 2018
Sponsor:
Collaborators:
European Commission
Firalis SA
University Hospital, Strasbourg
Centre Hospitalier Universitaire Vaudois
IRCCS Centro San Giovanni di Dio Fatebenefratelli
Hôpitaux Civils de Colmar
Istanbul University
Assistance Publique - Hôpitaux de Paris
University Hospital, Lille
University Hospital, Geneva
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Erasme University Hospital
University Hospital, Montpellier
Centre Hospitalier Universitaire de Besancon
Centre Hospitalier Universitaire de Nice
Information provided by (Responsible Party):
Amoneta Diagnostics SAS

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).

Condition or disease
Alzheimer Disease (AD) Frontotemporal Lobar Degeneration Dementia With Lewy Bodies (DLB) Parkinson Disease Dementia (PDD) Progressive Supranuclear Palsy (PSP) Corticobasal Degeneration (CBD)

  Show Detailed Description

Layout table for study information
Study Type : Observational
Estimated Enrollment : 800 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Multi-centre Proof-of-performance Clinical Study to Validate Blood-based Biomarker Candidates for the Diagnosis of Alzheimer's Disease
Study Start Date : January 2017
Estimated Primary Completion Date : March 2019
Estimated Study Completion Date : March 2019


Group/Cohort
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
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)
Healthy Controls
200 healthy subjects



Primary Outcome Measures :
  1. Blood cell biomarkers for diagnosis of Alzheimer [ Time Frame: 18 Months ]
    Proof of Performance of ADDIA' blood biomarker-based test


Secondary Outcome Measures :
  1. Biomarkers circulating in body fluids for diagnosis of Alzheimer and/or other dementia type [ Time Frame: 18 months ]
    Validation of biomarkers circulating in peripheral body fluids


Biospecimen Retention:   Samples With DNA
Blood


Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   40 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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).
Criteria

Inclusion Criteria:

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:

For all patients of the group NAD, except PSP subgroup (when PSP has a clear-cut typical phenotype, sometimes called Steele-Richardson phenotype), the CSF biomarker data must show levels for CSF biomarkers Aβ1-42, phosphorylated-Tau and total-Tau, compatible with the respective NAD subgroup. If retrospective CSF data are not available, retrospective Aβ PET and Tau PET data can be used.

Fronto-temporal dementia (FTD)

  • Diagnosis of probable behavioural FTD (bvFTD) for all subjects of this FTD subgroup, whether with familial or non-familial forms. If with familial form, the subject must be a member of family with a known mutation in one of the FTD related genes: MAPT, PGRN. The predominant phenotype in the kindred must be cognitive/behavioural (i.e. kindred in whom Parkinsonism or Amyotrophic Lateral Sclerosis is the predominant clinical phenotype among affected relatives is excluded).
  • Centrally rated frontal and/or anterior temporal atrophy score of 2 or greater on brain MRI.
  • MMSE score compatible. If currently taking an acetylcholinesterase inhibitor and/or memantine, the subject must have been taking such medication(s) for ≥3 months.

Dementia Lewy body (DLB)

  • DLB should be diagnosed when dementia occurs before or concurrently with Parkinsonism.
  • Patients diagnosed with probable DLB. Probable DLB can be made with the presence of two core features out of the following:

    • Fluctuating cognition with pronounced variations in attention and alertness,
    • Recurrent visual hallucinations that are typically well formed and detailed,
    • Spontaneous features of Parkinsonism.

Probable DLB is diagnosed with the presence of one or more of the above core features and one or more of the following suggestive features. Probable DLB should not be diagnosed on the basis of suggestive features alone:

  • REM sleep behaviour disorder,
  • Severe neuroleptic sensitivity,
  • Low dopamine transporter uptake in basal ganglia demonstrated by SPECT or PET imaging (if data retrospectively available).

Supportive diagnosis:

  • Generalized low uptake on SPECT/PET perfusion scan with reduced occipital activity (if data retrospectively available),
  • Abnormal (low uptake) MIBG myocardial scintigraphy,
  • Prominent slow wave activity on EEG with temporal lobe transient sharp waves.

    • MRI: Relative preservation of medial temporal lobe structures on CT/MRI scan.
    • Clinical Dementia Rating (CDR) score is greater than or equal to 0.5.
    • MMSE score compatible.
    • Patients with familial forms caused by mutation in genes SNCA, SNCB.

Parkinson's disease dementia (PDD)

  • Subjects with Parkinson's Disease Dementia (PDD) must have dementia after (not before) developing Parkinson's disease (PD).
  • PD is diagnosed by the 3 typical PD symptomatic findings:

    • tremor,
    • rigidity, and
    • slowed movement (bradykinesia).
  • Subjects with dementia and with LRRK2 gene mutation (or with mutation in one of the following genes: PARK2 or SNCA, VPS35, PINK1, DJ1, ATP13A2, FBX07, SLC6A3, TAF1 are also included.
  • L-DOPA responsive (a good response to levodopa as practiced by clinical investigator, retrospectively to the study).
  • MMSE score < 21 for moderate to severe PDD and > 21 for mild PDD.
  • MRI: evidence of relevant structural abnormality (i.e. basal ganglia for Parkinsonism and potentially medio-temporal or cortical findings that may be related to dementia). Functional imaging techniques such as fluoro-dopa PET, FDG PET or SPECT to document the presence of dopaminergic dysfunction if retrospectively available.

Progressive Supranuclear Palsy (PSP)

  • Diagnosis of probable or possible PSP as defined by the National Institute of Neurological Disorders and Stroke and Society for Progressive Supranuclear Palsy (NINDS-SPSP) diagnostic criteria, and as summarized by Armstrong et al. (2013) for the conclusions on CBD criteria from an international consortium of behavioural neurology, neuropsychology, and movement disorders specialists):

    • Gradually progressive disorder,
    • Onset at age 40 or later,
    • Vertical (upward or downward gaze) supranuclear palsy and prominent postural instability with tendency to fall in the first year of disease onset,
    • No evidence of other diseases that could explain the foregoing features, as indicated by mandatory exclusion criteria.
  • 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)

• Diagnosis of possible CBD. Inclusion clinical criteria for possible CBD, with features of Cortico-Basal Syndrome (CBS); familial forms related to MAPT included, Progressive Supranuclear Palsy Syndrome (PSPS) phenotype included.

  • 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.
  • If retrospectively available, Aβ PET and/or Tau PET scan(s) shall be negative.
  • Able to comply with the study procedures.

EXCLUSION CRITERIA for all subjects:

The following exclusion criteria apply to all subjects:

  • Neutropenia (Neutrophils: < 1,500/mm3 according to ethnic group).
  • Thrombocytopenia (platelets: < 100,000/mm3, rule out EDTA-induced pseudo-thrombocytopenia).
  • Subjects with less than an elementary education are excluded.
  • Subject with no medical insurance are excluded in the countries where medical insurance is mandatory such as in France. In the countries where medical insurance is not mandatory, subjects with no medical insurance may not be excluded.
  • Psychiatric history: schizophrenia, psychosis.
  • Vascular dementia.
  • Infection diseases, chronic inflammatory diseases that affect blood cells, patients with an active infection/ immunosuppressive disorders/ treatment with immunosuppressive or immunomodulatory medication.
  • Current malignancy or past diagnosis of malignancy affecting blood cells under treatment or with treatment stopped only during last 3 months.
  • Medication interfering with cognitive functions and ADDIA biomarkers (i.e. kinase inhibitors and beta-amyloid and tau passive and active immunizations).
  • Major sensory deficits that could interfere with cognitive assessment (visual and auditory).
  • Epilepsy.
  • Patients with known contraindication for MRI imaging such as MRI-incompatible stent or MRI-incompatible endoprosthesis.

EXCLUSION CRITERIA for AD group

  • Mixed dementia.
  • Vascular dementia.
  • Other dementia type.
  • Other neurodegenerative disease.
  • Absence of CSF biomarker data and/or amyloid PET data is an exclusive criterion for all subjects with sporadic forms of AD, but it is not an exclusive criterion for subjects with a familial form of AD that is due to a mutation of a gene among APP, PSEN1, PSEN2.

EXCLUSION CRITERIA for NAD group

  • AD diagnosis.
  • Mixed dementia.
  • Vascular dementia.
  • Absence of either CSF biomarker data or amyloid PET data is an exclusive criterion for all subjects in sporadic DLB, PDD, FTD and CBD (but not for subjects with PSP when PSP has a clear-cut typical phenotype, sometimes called Steele-Richardson phenotype). However, absence of CSF biomarker and/or amyloid PET data is not an exclusive criterion for subjects with a familial form of NAD that is due to a mutation of a gene among MAPT, PGRN, SNCA, SNCB, PARK2 or SNCA, VPS35, PINK1, DJ1, ATP13A2, FBX07, SLC6A3 or TAF1, TREM2.

EXCLUSION CRITERIA for Control group

  • AD patients.
  • Dementia patients.
  • Cognitive impairments.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03030586


Contacts
Layout table for location contacts
Contact: Saliha Moussaoui, PhD 33389911321 saliha.moussaoui@firalis.com
Contact: Hüseyin Firat, MD 33389911321 hueseyin.firat@firalis.com

Locations
Layout table for location information
Belgium
Cliniques Universitaires Saint-Luc Recruiting
Brussels, Belgium
Contact: Adrian Ivanoiu, MD         
ERASME Hospital Recruiting
Brussels, Belgium
Contact: Jean-Christophe Bier, MD         
France
Hopitaux Universitaires de Strasbourg Recruiting
Strasbourg, Alsace, France
Contact: Frédéric Blanc, MD    33388115858    frederic.blanc@chru-strasbourg.fr   
Centre Hospitalier Universitaire de Besançon Recruiting
Besançon, France
Contact: Eloi Magnin, MD         
Hôpitaux Civils (Hopital Louis Pasteur) de Colmar Recruiting
Colmar, France
Contact: François Sellal, MD         
Centre Hospitalier Régional Universitaire de Lille Recruiting
Lille, France
Contact: Florence Pasquier, MD         
Centre Hospitalier Universitaire de Montpellier Recruiting
Montpellier, France
Contact: Audrey Gabelle, MD         
Centre Hospitalier Universitaire de Nice Recruiting
Nice, France
Contact: Renaud David, MD         
APHP-Hôpitaux Universitaires Pitié Salpêtrière Recruiting
Paris, France
Contact: Bruno Dubois, MD         
Italy
IRCCS Centro San Giovanni di Dio Fatenenefratelli Recruiting
Brescia, Italy
Contact: Moira Marizzoni, PhD         
Switzerland
Hôpitaux Universitaires de Genève Recruiting
Genève, Switzerland
Contact: Giovanni Frisoni, MD         
Centre Hospitalier Universitaire Vaudois Recruiting
Lausanne, Switzerland
Contact: Jean-François Démonet, MD         
Turkey
Istanbul University Hospital Recruiting
Istanbul, Turkey
Contact: Hakan Gurvit, MD         
Sponsors and Collaborators
Amoneta Diagnostics SAS
European Commission
Firalis SA
University Hospital, Strasbourg
Centre Hospitalier Universitaire Vaudois
IRCCS Centro San Giovanni di Dio Fatebenefratelli
Hôpitaux Civils de Colmar
Istanbul University
Assistance Publique - Hôpitaux de Paris
University Hospital, Lille
University Hospital, Geneva
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Erasme University Hospital
University Hospital, Montpellier
Centre Hospitalier Universitaire de Besancon
Centre Hospitalier Universitaire de Nice
Investigators
Layout table for investigator information
Principal Investigator: 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 Hôpitaux Universitaires de Genève
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

Layout table for additonal information
Responsible Party: Amoneta Diagnostics SAS
ClinicalTrials.gov Identifier: NCT03030586     History of Changes
Other Study ID Numbers: ST0056
First Posted: January 25, 2017    Key Record Dates
Last Update Posted: December 5, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Amoneta Diagnostics SAS:
Blood cell biomarkers, peripheral circulating biomarkers

Additional relevant MeSH terms:
Layout table for MeSH terms
Dementia
Lewy Body Disease
Parkinson Disease
Alzheimer Disease
Supranuclear Palsy, Progressive
Frontotemporal Lobar Degeneration
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Tauopathies
Neurocognitive Disorders
Mental Disorders
Ophthalmoplegia
Ocular Motility Disorders
Cranial Nerve Diseases
Paralysis
Neurologic Manifestations
Eye Diseases
Signs and Symptoms
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases