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

NCT ID: NCT05306834

Last Updated: 2024-01-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

400 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-11-10

Study Completion Date

2027-11-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

cSVD is by far the most prevalent vascular contributor to cognitive impairment in the population. However, accurate quantitative estimates of the predictive ability of cSVD for dementia risk are lacking. Moreover, stratification of cognitive decline and dementia risk in cSVD patients according to imaging characteristics as well as evidence of coexisting neurodegenerative disease and vascular comorbidity are lacking. Hypertension is the strongest known risk factor for cSVD but there are currently no guidelines for the management of cSVD (or emerging guidelines based on weak evidence, and no specific mechanism-based treatments, leading to empirical and heterogeneous clinical practice, which in most instances consists of ignoring these lesions. This clinical blind spot represents a major "missed opportunity" for the prevention of cognitive decline and dementia.

This study aims to explore the relation of brain and retinal microvasculature image characteristics (imaging biomarkers), as well as molecular biomarkers derived from blood, with presence or absence of extensive cSVD and with cognitive and other clinical characteristics in two groups of 200 patients 60+ years of age. The first group will consist of patients with little or no white matter hyperintensities on brain MRI (no or minor MRI features of cSVD); while the second will include patients with moderate to severe white matter hyperintensities (MRI features of extensive cSVD).

This will create a unique deeply characterized resource for epidemiological and mechanistic investigations of cSVD, which can also serve as a pilot setting to test the trajectories and requirements for individualized patient care of cSVD patients.

The combination of retinal microvascular measurements using innovative multimodal imaging is entirely novel to our knowledge. In the context of the RHU SHIVA program, the same retained imaging protocol will be implemented for 400 young adults, which will provide insight into trajectories of these retinal biomarkers across the adult lifespan).

For the molecular biomarkers allow the validation of genomic, epigenomic, transcriptomic, proteomic, and metabolomic biomarkers for cSVD identified through secondary use of large existing cohort studies in the general population (3C, i-Share cohorts), in persons with memory complaints (MEMENTO cohort), and in collaboration with other cohorts with the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, also as part of the RHU SHIVA program.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Cerebral Small Vessel Diseases Stroke Dementia

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Minimal cSVD patient group

little or no white matter hyperintensities

Group Type ACTIVE_COMPARATOR

Retinal Imaging

Intervention Type PROCEDURE

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

Blood sample

Intervention Type GENETIC

Analyses of molecular biomarkers including

Evaluation of cardiovascular risks

Intervention Type PROCEDURE

Measurement of blood pressure and arterial stiffness

Brain imaging (MRI)

Intervention Type PROCEDURE

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

Cognitive Tests

Intervention Type 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)

Geriatric Depression Scale (GDS)

Intervention Type OTHER

15 items

Instrumental Activities of Daily Living (IADL)

Intervention Type OTHER

Instrumental Activities of Daily Living (IADL)

Unipodal standing test

Intervention Type DIAGNOSTIC_TEST

Unipodal standing test

Walking speed measurement

Intervention Type OTHER

over 5 meters

Extensive cSVD patient group

moderate to severe white matter hyperintensities

Group Type ACTIVE_COMPARATOR

Retinal Imaging

Intervention Type PROCEDURE

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

Blood sample

Intervention Type GENETIC

Analyses of molecular biomarkers including

Evaluation of cardiovascular risks

Intervention Type PROCEDURE

Measurement of blood pressure and arterial stiffness

Brain imaging (MRI)

Intervention Type PROCEDURE

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

Cognitive Tests

Intervention Type 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)

Geriatric Depression Scale (GDS)

Intervention Type OTHER

15 items

Instrumental Activities of Daily Living (IADL)

Intervention Type OTHER

Instrumental Activities of Daily Living (IADL)

Unipodal standing test

Intervention Type DIAGNOSTIC_TEST

Unipodal standing test

Walking speed measurement

Intervention Type OTHER

over 5 meters

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Retinal Imaging

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

Intervention Type PROCEDURE

Blood sample

Analyses of molecular biomarkers including

Intervention Type GENETIC

Evaluation of cardiovascular risks

Measurement of blood pressure and arterial stiffness

Intervention Type PROCEDURE

Brain imaging (MRI)

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

Intervention Type PROCEDURE

Cognitive Tests

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)

Intervention Type OTHER

Geriatric Depression Scale (GDS)

15 items

Intervention Type OTHER

Instrumental Activities of Daily Living (IADL)

Instrumental Activities of Daily Living (IADL)

Intervention Type OTHER

Unipodal standing test

Unipodal standing test

Intervention Type DIAGNOSTIC_TEST

Walking speed measurement

over 5 meters

Intervention Type OTHER

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

For the extensive cSVD patient group

1. 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"),
* Free, informed and written consent signed by the participant and the investigator (at the latest on the day of inclusion and before any examination required by the research study).
2. For the extensive cSVD patient group not included in the LEOPOLD trial:

* Patients aged 60 to 88 years,
* Patients with a cognitive complaint MMSE ≥ 20 performed in the 6 months before inclusion, associated or not with impaired cognitive tests and/or diaognosis of incipient dementia without pronounced cognitive deterioration,
* Patients with a socio-educational level ≥ 3,
* Patients with a moderate to high grade of hypersignals on an MRI OR on an CT scan performed prior inclusion (grades C and D of the modified Scheltens scale or grade 2/3 Fazekas),
* Arterial hypertension defined by a Systolic Blood Pressure (SBP) and / or Diastolic Blood Pressure (DBP) ≥ 140/90 mmHg (according to the definition of the national health authority \[HAS\]), treated or not, confirmed within the previous 12 months or at the latest on the day of inclusion.
* Being affiliated or beneficiary of the French national health insurance ("sécurité sociale"),
* Free, informed and written consent signed by the participant and the investigator (at the latest on the day of inclusion and before any examination required by the research study)

For the minimal cSVD patient group:

* Patients aged 60 to 88 years,
* Patients with a cognitive complaint (MMSE ≥ 20 performed at the SHIVA inclusion visit or in the 6 monts prior the visit) associated or not with impaired cognitive tests and/or diagnosis of incipient dementia without pronounced cognitive deterioration,
* Patients with little or no white matter hypertensities on brain MRI (grades 0 or 1 on the Fazekas scale); without lacunes or microbleeds,
* Arterial hypertension defined by a Systolic Blood Pressure (SBP) and / or Diastolic Blood Pressure (DBP) ≥ 140/90 mmHg (according to the definition of the national health authority \[HAS\]), treated or not, confirmed within the previous 12 months or at the latest on the day of inclusion. Blood pressure values for this inclusion criterion can be objectified by several self-measurements performed by the patient at home for 3 days in a sitting or lying position (3 measurements on sitting or lying position and 3 measurements in standing position).
* Being affiliated or beneficiary of the French national health insurance ("sécurité sociale"),
* Free, informed and written consent signed by the participant and the investigator (at the latest on the day of inclusion and before any examination required by the research study

Exclusion Criteria

For Extensive cSVD patient group :

1. 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
2. For the extensive cSVD patient group not included in the LEOPOLD trial:

* Orthostatic hypotension defined by a decrease of 20 mmHg in SBP and / or 10 mmHg in DBP in a standing position at 3 minutes sought in the previous 3 months or on the day of inclusion,
* 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)
* patients with severe myopia greater than -6 dioptres
* participants with known allergy to Tropicamide (Mydriaticum®)
* patients with an extensive cataract
* patients with ptosis

For the minimal cSVD patient group:

* Orthostatic hypotension defined by a decrease of 20 mmHg in SBP and / or 10 mmHg in DBP in a standing position at 3 minutes sought in the previous 3 months or on the day of inclusion,
* 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)
* Patients with severe myopia greater than -6 dioptries
* Patients with known allergy to Tropicamide (Mydriaticum®)
* Patients with an extensive cataract
* Patients with ptosis
Minimum Eligible Age

60 Years

Maximum Eligible Age

88 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

University Hospital, Bordeaux

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Olivier HANON, Pr

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Marc JOLIOT, Dr

Role: STUDY_CHAIR

Unité CNRS UMR5296, Groupe d'Imagerie

Cécile DELCOURT, Dr

Role: STUDY_CHAIR

Centre INSERM U1219 Bordeaux Population Health

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Bordeaux Hospital

Bordeaux, , France

Site Status RECRUITING

Broca Hospital

Paris, , France

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

France

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Stéphanie DEBETTE, Pr

Role: CONTACT

5.57.57.16.59 ext. +33

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

DEBETTE Stéphanie, Pr

Role: primary

HANON Olivier, Pr

Role: primary

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

CHUBX 2021/22

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Neurothrombectomy France
NCT02880579 COMPLETED