Establishment of a CSF Bank for the Development of Biomarkers of Smooth Muscle Cell (SMC) Damage in Monogenic Cerebral Small Vessel Disease (CSF-cSVD)

Assistance Publique - Hôpitaux de Paris

Status: Not yet enrolling

Conditions: Cerebral Small Vessel Diseases; CADASIL (Diagnosis)

Treatments: Other: Cerebrospinal fluid (CSF) sample and additional blood samples

Study type: Observational

Funder types: Other

Identifiers

NCT05793424

APHP220744

Details and patient eligibility

About

The main objective of this research is to obtain biological markers of smooth muscle cells dysfunction or degeneration in cerebral small vessel diseases.

The aim of this research is therefore to build up a biocollection of CSF and blood samples from 1) patients with CADASIL disease (the most common form of cSVD) responsible for an accumulation of the NOTCH3 protein in the microvessel wall, 2) patients with other forms of monogenic cSVD (rarer) which are not responsible for an accumulation of this protein despite the damage to the smooth muscle cells of the vessel wall and 3) control patients without cSVD, collected in the context of care.

This bio-collection will allow the identification and assay of markers testifying to the damage of the smooth muscle cells (SMC) in different types of cSVD of hereditary origin, the first of which will be the soluble NOTCH3 protein.

Enrollment: 90 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

For patients woth monogenic cSVD :

Inclusion Criteria:

• Patients aged between 18 and 80 years at the time of inclusion
• Diagnosis confirmed by detection of a pathogenic mutation in the NOTCH3 gene characteristic of CADASIL, or in another gene responsible for other forms of monogenic cSVD (such as COL4A1, COL4A2, HTRA1).
• Beneficiary of a social security system
• Having given their written consent

Non inclusion Criteria:

• Contraindication to lumbar puncture:
• Haemostasis disorder (severe thrombocytopenia <60,000/mm3, PT abnormalities, INR>1.5 and/or aPTT>1.5) or anticoagulant use.
• Spinal plaque in or near the lumbar region (surgery) that may interfere with CSF collection
• Behavioural disorder that may interfere with the sampling process
• Intracranial process, intracranial hypertension or risk of involvement on imaging
• Skin lesions (inflammation or infection of any kind) or developmental abnormality (myelomeningocele) adjacent to the puncture site
• Person referred to in articles L. 1121-5 to L. 1121-8 and L. 1122-12 of the public health code, defined as :
• Pregnant, parturient or breastfeeding woman
• Person deprived of liberty by judicial or administrative decision
• Person hospitalised without consent and not subject to a legal protection measure, and person admitted to a health or social establishment for purposes other than research
• Minor
• Person of full age subject to a legal protection measure (guardianship, curators or safeguard of justice), person of full age unable to express their consent and not subject to a protection measure
• Person subject to an exclusion period for another research
• Patients participating in other interventional research
• Contraindication to lumbar puncture:
• Haemostasis disorder (severe thrombocytopenia <60,000/mm3, PT abnormalities, INR>1.5 and/or aPTT>1.5) or anticoagulant use.
• Spinal plaque in or near the lumbar region (surgery) that may interfere with CSF collection
• Spinal plaque (surgery)
• Behavioural disorder that may interfere with the sampling process
• Intracranial process, intracranial hypertension or risk of involvement on imaging
• Skin lesions (psoriasis, infection....)inflammation or infection of any kind) or developmental abnormality (myelomeningocele) adjacent to the puncture site
• Person referred to in articles L. 1121-5 to L. 1121-8 and L. 1122-12 of the public health code, defined as
• Pregnant, parturient or breastfeeding woman
• Person deprived of liberty by judicial or administrative decision
• Person hospitalised without consent and not subject to a legal protection measure, and person admitted to a health or social establishment for purposes other than research
• Minor
• Person of full age subject to a legal protection measure (guardianship, curators or safeguard of justice), person of full age unable to express their consent and not subject to a protection measure
• Person subject to an exclusion period for another research
• Patients participating in other interventional research

For control patients ( selection after CSF sampling):

Inclusion criteria :

• Subject aged 18-80 years at the time of inclusion
• Imaging done: strictly normal CT scan OR MRI showing no abnormality suggestive of cSVD
• Beneficiary of a social security system
• Having had CSF and blood samples taken as part of the treatment
• Agreement to use blood and CSF samples remainders for research purposes (information and non-opposition).
• Women who were pregnant at the time the samples were taken will not be offered to participate in the study

Non inclusion criteria :

• Any previously identified intracranial vascular pathology requiring specific management (vasculitis, acute reversible angiopathy, severe intracranial atheroma)
• Acute or chronic infectious disease (meningitis or meningoencephalitis)
• Known pregnancy
• Persons participating in other interventional research
• Preparation and freezing time for blood and CSF samples is more than 4 hours

Trial design

90 participants in 2 patient groups

Patients with cerebral small vessel disease ( cSVD)

Treatment:

Other: Cerebrospinal fluid (CSF) sample and additional blood samples

Control patients