Stopping Cognitive Decline and Dementia by Fighting Covert Cerebral Small Vessel Disease

NCT05306834 | Recruiting

• 1 other identifier: CHUBX 2021/22
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 2

Brief Summary

Cerebral small Vessel Disease (cSVD), characterized by an alteration of the structure and function of small penetrating brain arteries, is highly prevalent in older persons from the general population and represents a leading cause of stroke and a major contributor to cognitive decline and dementia risk. In France \>4 million persons aged 60+ are estimated to have moderate to extensive covert cSVD (ccSVD), i.e. features of SVD on brain imaging without a history of clinical stroke. Better detection and management of covert cSVD would have a major impact on preventing disability and costs related to stroke, cognitive impairment and dementia. However, there are no specific mechanistic treatments for cSVD and hardly any recommendations worldwide on how to prevent and treat cSVD and related cognitive impairment. The aim of the present study, through the identification of novel cutting-edge multimodal biomarkers, is to develop innovative diagnostic and risk prediction tools for cSVD and its complications and to contribute to accelerating the discovery of novel drug targets and therapeutics strategies for cSVD.

Conditions

Cerebral Small Vessel Diseases; Stroke; Dementia

Keywords

Cognitive decline; Dementia; Stroke; Small vessel disease; Healthy brain aging; Brain imaging; Adaptive optics; Optical coherence tomography angiography; Prevention; Risk prediction; Genomic; Multiomics; Proteomics; Metabolomics

Outcome Measures

Primary Outcomes (1)

• Comparison of images and the molecular data

  This comparison should help identify relevant biomarkers to characterize and categorize cSVD. We will also more broadly look at the association of retinal microvascular markers and molecular biomarkers with all available MRI-markers of cSVD (beyond the presence or absence of extensive white matter hyperintensities that defines the cases and controls).

  Day 0 and Year 3

Secondary Outcomes (7)

• Degree of association between retinal and brain marker

  Day 0, Year 1 and Year 3

• Degree of association between brain, microvascular and retinal marker

  Day 0, Year 1, Year 2 and Year 3

• Correlation between retinal micovascular biomarkers

  Day 0, Year 1, Year 2 and Year 3

• Reproducibility and time course of retinal vascular biomarkers

  Between Day 0 and Year 1

• Detecting, classifying and quantifying markers of retinal microvascular lesions

  up to year 3

Study Arms (2)

Minimal cSVD patient group

ACTIVE COMPARATOR

little or no white matter hyperintensities

Procedure: Retinal Imaging; Genetic: Blood sample; Procedure: Evaluation of cardiovascular risks; Procedure: Brain imaging (MRI); Other: Cognitive Tests; Other: Geriatric Depression Scale (GDS); Other: Instrumental Activities of Daily Living (IADL); Diagnostic Test: Unipodal standing test; Other: Walking speed measurement

Extensive cSVD patient group

ACTIVE COMPARATOR

moderate to severe white matter hyperintensities

Procedure: Retinal Imaging; Genetic: Blood sample; Procedure: Evaluation of cardiovascular risks; Procedure: Brain imaging (MRI); Other: Cognitive Tests; Other: Geriatric Depression Scale (GDS); Other: Instrumental Activities of Daily Living (IADL); Diagnostic Test: Unipodal standing test; Other: Walking speed measurement

Interventions

Retinal Imaging PROCEDURE

Auto-Refractometry / Adaptative Optics (OA) / Swept Source Optical Coherence Tomography (SS-OCT-A) / Globe Axial length measurements / Color Retinophotography of the retina.

Extensive cSVD patient group; Minimal cSVD patient group

Blood sample GENETIC

Analyses of molecular biomarkers including

Extensive cSVD patient group; Minimal cSVD patient group

Evaluation of cardiovascular risks PROCEDURE

Measurement of blood pressure and arterial stiffness

Extensive cSVD patient group; Minimal cSVD patient group

Brain imaging (MRI) PROCEDURE

3DT1 / 3DFLAIR / T2GRE / DTI 15 directions (and B0MAP)

Extensive cSVD patient group; Minimal cSVD patient group

Cognitive Tests OTHER

Mini Mental State Examination (MMSE) / Montreal Cognitive Assessment (MoCA) / 16 items Free and Cued Recall (RL/RI 16 items) / Trail Making Test A et B (TMT A et B) / Frontal Assessment Battery (FAB) / Phonemic (letter P) and semantic (animals) verbal fluency tests / Digit Symbol Substitution Test (DSST)

Extensive cSVD patient group; Minimal cSVD patient group

Geriatric Depression Scale (GDS) OTHER

15 items

Extensive cSVD patient group; Minimal cSVD patient group

Instrumental Activities of Daily Living (IADL) OTHER

Instrumental Activities of Daily Living (IADL)

Extensive cSVD patient group; Minimal cSVD patient group

Unipodal standing test DIAGNOSTIC_TEST

Unipodal standing test

Extensive cSVD patient group; Minimal cSVD patient group

Walking speed measurement OTHER

over 5 meters

Extensive cSVD patient group; Minimal cSVD patient group

Eligibility Criteria

• Age: 60 Years - 88 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For the extensive cSVD patient group
• For the extensive cSVD patient group included in the LEOPOLD trial:
• Patients aged 60 to 88 years,
• Patients included in the LEOPOLD trial and having performed their brain MRI on SIEMENS PRISMA machine
• Being affiliated or beneficiary of the French national health insurance ("sécurité sociale"),
• For the extensive cSVD patient group not included in the LEOPOLD trial:
• Patients aged 60 to 88 years,
• Patients with a socio-educational level ≥ 3,
• Being affiliated or beneficiary of the French national health insurance ("sécurité sociale"),
• For the minimal cSVD patient group:
• Patients aged 60 to 88 years,
• Patients with little or no white matter hypertensities on brain MRI (grades 0 or 1 on the Fazekas scale); without lacunes or microbleeds,
• Being affiliated or beneficiary of the French national health insurance ("sécurité sociale"),

You may not qualify if:

• For Extensive cSVD patient group :
• For the extensive cSVD patient group also included in the LEOPOLD trial:
• patients with severe myopia greater than -6 dioptres
• partients with known allergy to Tropicamide (Mydriaticum®)
• patients with an extensive cataract
• patients with ptosis
• For the extensive cSVD patient group not included in the LEOPOLD trial:
• Very severe renal impairment (creatinine clearance less than 15 ml / min) on a blood test dating back less than one year,
• Secondary hypertension: renovascular hypertension, primary hyperaldosteronism, pheochromocytoma...
• Contraindication to MRI (presence of a ferromagnetic foreign body, in particular certain intracranial clips, certain heart valves, an intraocular foreign body, metal prosthesis, subject carrying a pacemaker, subject carrying prosthetic heart valves incompatible with MRI. ventricular shunt, claustrophobia),
• Associated severe diseases, with a life expectancy of less than 3 months,
• Physical problems likely to interfere with the feasibility of the tests (sight, hearing, etc.),
• Existence of dementia of which the etiology is distinct from Alzheimer's disease, vascular or mixed dementia
• Persons under tutorship or curatorship,
• Patients with loss of autonomy living in EHPAD (nursing home)

Sponsors & Collaborators

• University Hospital, Bordeaux: lead

Study Sites (2)

Bordeaux Hospital

Bordeaux, 33000, France

RECRUITING

Broca Hospital

Paris, 75014, France

RECRUITING

MeSH Terms

Conditions

Cerebral Small Vessel Diseases; Stroke; Dementia; Cognitive Dysfunction

Interventions

Blood Specimen Collection; Neuroimaging; Magnetic Resonance Spectroscopy; Neuropsychological Tests

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Diagnostic Imaging; Diagnostic Techniques, Neurological; Spectrum Analysis; Chemistry Techniques, Analytical; Psychological Tests; Behavioral Disciplines and Activities

Study Officials

• Olivier HANON, Pr

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

• Marc JOLIOT, Dr

  Unité CNRS UMR5296, Groupe d'Imagerie

  STUDY CHAIR

• Cécile DELCOURT, Dr

  Centre INSERM U1219 Bordeaux Population Health

  STUDY CHAIR

Central Study Contacts

Stéphanie DEBETTE, Pr

CONTACT

5.57.57.16.59; stephanie.debette@u-bordeaux.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2022
• First Posted: April 1, 2022
• Study Start: November 10, 2022
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: January 26, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2)