Taxonomy of Neurodegenerative Diseases : Observational Study in Alzheimer's Disease and Parkinson's Disease

NCT05040048 | Completed

• 2 other identifiers: 14-372015-A00356-43
• Study Type: observational
• Target: 220
• Locations: 4 countries
• Sites: 4

Brief Summary

The AETIONOMY project will generate a refined taxonomy and testable mechanisms underlying the derived stratification of patients.

Conditions

Alzheimer's Disease; Parkinson's Disease

Keywords

Alzheimer; Parkinson; Data mining; Biomarkers; Stratification

Outcome Measures

Primary Outcomes (1)

• Performance of the biomarker in discriminating between the taxonomy of interest and the remainder of the AD/PD subjects

  assessments of the effectiveness of a biomarker in assigning a taxonomy will be made using subjects with the taxonomy membership of interest and the Healthy Controls. biomarkers), surrogate of a causative mechanism for PD or AD (2 biomarkers for each disease). AETIONOMY is built to validate the mechanism-based stratification of patients by testing in real clinical samples the hypotheses underlying pathogenic mechanisms identified by the consortium. It is expected to assess a large panel of biomarkers exploring biocollections (blood, DNA, CSF, skin biopsies) and imaging, associated with clinical assessment: (Pathway-Material for assessment (planned biomarker)) Astroglial inflammation-CSF(YKL40) Neuroinflammation-CSF and/or blood(MRP8, MRP14) Cross-talk mitochondria/neuroinflammation-CSF(TFAM, HSD10) Epigenetics-DNA(SNCA methylation) Insulin pathway-CSF and/or blood(IRS) Stress-induced comorbidity-DNA(CRH, CRHR1, MAPT) Uptake of aggregate proteins-material TBD(Syndecan)

  27 months

Study Arms (2)

Parkinson's disease Group

Blood, cerebrospinal fluid (CSF) and skin biopsy samples. Neuropsychological assessment. Motor and non motor assessments for Parkinson's disease group only.

Other: Clinical, biological and imaging assessment

Alzheimer's disease Group

Blood, cerebrospinal fluid (CSF) and skin biopsy samples. Neuropsychological assessment. Brain MRI for Alzheimer's disease group only.

Other: Clinical, biological and imaging assessment

Interventions

Clinical, biological and imaging assessment OTHER

Alzheimer's disease Group; Parkinson's disease Group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

PD GROUP (n=325): * 240 idiopathic PD patients * 40 PD patients with mutations of the gene of Parkin (n =10), LRRK2 (n=10) and GBA (n=20) * 45 subjects at risk of PD: * first degree relative of a PD index case with mutation (LRRK2, n=10) * first degree relative of a PD index case with risk factor (GBA, n=10) * subjects with idiopathic RBD (n=25) AD GROUP (n=150): * 90 prodromal AD patients * 60 preclinical AD patients HEALTHY CONTROLS (n=180): * 90 healthy controls matched for age and sex for PD group's subject * 90 healthy controls matched for age and sex for AD group's subject

You may qualify if:

• FOR ALL
• Male or female.
• Ability to provide written informed consent in accordance with International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH), Good Clinical Practice (GCP) and local regulations.
• Have social security insurance (for French patients only).
• PARKINSON'S DISEASE GROUP
• Idiopathic PD patients:
• ≤ Age ≤75 years.
• Diagnosed as "clinically possible", "clinically probable" or "clinically definite" idiopathic PD according to UK Parkinson's Disease Society Brain Bank (UKPDSBB, Hugues et al. 1992).
• PD patients with mutation in Parkin, Leucine-rich repeat kinase 2 (LRRK2) or Glucosidase beta acid (GBA) gene:
• Age ≥ 18 years.
• Diagnosed with PD and genotyped for a mutation in Parkin, LRRK2 or GBA genes.
• Subjects at risk of PD:
• Age ≥ 18 years.
• No clinical symptom of PD at neurological examination (akinesia, no extrapyramidal rigidity, and no rest tremor).
• One of the following criteria: First-degree relative of a PD index case with a LRRK2 or GBA mutation OR Idiopathic Rapid eye movement (REM) Behavior Disorder (RBD) as defined by the presence of at least 1 of the following conditions: (1) Potentially harmful dream-enacting behaviors in response to dream content and loss of normal electromyographic (EMG) atonia on polysomnography (PSG) manifest as sustained muscle activity during more that 27% of REM sleep in the chin EMG; (2) Abnormal behavior during REM sleep .

You may not qualify if:

• FOR ALL
• Anti-inflammatory
• Anti-neoplastic
• Immunosuppressives
• Systemic corticosteroids
• On-going viral or bacterial infection requiring at least symptomatic treatment, or antibiotics, or associated with fever or pain.
• Any psychiatric condition, which in the opinion of the investigator might preclude participation.
• Any lab abnormality, which in the opinion of the investigator might preclude participation.
• Pregnant woman or lactating or planning pregnancy during the course of the study (Includes a negative urine pregnancy test or to be of non-child bearing potential).
• Participant who does not wish to be informed of any clinically relevant abnormalities (as determined by the investigator at that site) identified during the course of the study (For France only).
• PARKINSON'S DISEASE GROUP
• Idiopathic PD patients:
• Family history of PD.
• Atypical PD syndromes due to either drugs (e.g., metoclopramide, flunarizine, neuroleptics) or metabolic disorders (e.g., Wilson's disease), encephalitis, or degenerative diseases (e.g., progressive supranuclear palsy).
• Currently taking neuroleptics or has taken neuroleptics within 6 months of baseline.

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead
• Innovative Medicines Initiative: collaborator
• Institut d'Investigacions Biomèdiques August Pi i Sunyer: collaborator
• ICM Co. Ltd.: collaborator
• University Hospital, Bonn: collaborator
• Karolinska Institutet: collaborator

Study Sites (4)

CIC Neurosciences - ICM - Hôpital Pitié-Salpêtrière, 47-83 Bd de l'Hôpital

Paris, 75013, France

Location

Universitaetsklinikum Bonn (UKB), Sigmund-Freud 25 Strasse

Bonn, 053105, Germany

Location

Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Rossello 149- 153

Barcelona, 08036, Spain

Location

Karolinska Institutet (KI), Karolinska University Hospital S3:01

Stockholm, 17176, Sweden

Location

Biospecimen

Retention: SAMPLES WITH DNA

blood and CSF samples

MeSH Terms

Conditions

Alzheimer Disease; Parkinson Disease

Interventions

Biological Products

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies

Intervention Hierarchy (Ancestors)

Complex Mixtures

Study Officials

• Jean-Christophe CORVOL, MD, PhD

  jean-christophe.corvol@aphp.fr

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2015
• First Posted: September 10, 2021
• Study Start: September 4, 2015
• Primary Completion: February 1, 2018
• Study Completion: February 1, 2018
• Last Updated: December 3, 2021

Record last verified: 2021-11

Locations

DE (1); FR (1); ES (1); SE (1)