HEMICOG: Severe Congenital Hemostatic Defects, Cerebral MIcrobleeds and COGnition

Sponsor

University Hospital, Lille (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06090201

Collaborator

(none)

200

Enrollment

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Cerebral microbleeds (CMBs) are haemosiderin deposits, resulting from the leakage of erythrocytes from small cerebral vessels, which can be detected noninvasively using susceptibility-sensitive magnetic resonance imaging (MRI) techniques. CMBs are commonly observed in daily practice: their prevalence range from five percent in healthy individuals over 65 years old to 50% in patients with a history of stroke. CMBs are associated with intracerebral hemorrhage (ICH) and also cognitive impairment and dementia.

The pathophysiology of CMBs is thought to primarily involve damage to brain microvasculature but the exact underlying cascade of events, including a potential role for haemostasis, has yet to be elucidated. Haemostatic defects (congenital or acquired) may contribute to an increased number and importance of CMBs. Congenital bleeding disorders such as haemophilia or von Willebrand disease (vWD), populations at high risk of ICH, are unique conditions that may give us further insights into a potential role of haemostatic defects in the pathophysiology of CMBs. CMBs might be the missing link between severe haemostatic defects, ICH risk and cognitive function.

We hypothesized that severe congenital haemostatic defects could contribute to an increased prevalence and number of CMBs, with an impact on cognition in adulthood.

Condition or Disease	Intervention/Treatment	Phase
Cerebral Microbleeds, Congenital Haemophilia, Congenital Von Willebrand Disease	Other: 3-Tesla brain MRI and a comprehensive neuropsychological assessment

Study Design

Study Type:

Observational

Anticipated Enrollment :

200 participants

Observational Model:

Cohort

Time Perspective:

Cross-Sectional

Official Title:

Cerebral Microbleeds in Severe Congenital Hemostatic Defects: Prevalence and Impact on Cognition

Anticipated Study Start Date :

Nov 1, 2023

Anticipated Primary Completion Date :

May 1, 2026

Anticipated Study Completion Date :

Aug 1, 2026

Outcome Measures

Primary Outcome Measures

The rate of patients with at least one CMB on 3-Tesla brain MRI (using specific sequences dedicated to the detection of CMBs). [Within 3 Months after inclusion]

Secondary Outcome Measures

Number and anatomical location (deep/lobar) of CMBs on 3-Tesla brain MRI [Within 3 Months after inclusion]
Multi-domain cognitive performances assessed by standardized scales as follows [Within 3 Months after inclusion]
- MoCA
Multi-domain cognitive performances assessed by standardized scales as follows [Within 3 Months after inclusion]
Memory: The free and cued selective reminding test (FCSRT, French version) ; The Wechsler digit span task will be used to examine verbal short term and working memory.
Multi-domain cognitive performances assessed by standardized scales as follows [Within 3 Months after inclusion]
- Processing speed and attention: digit symbol coding subtest of WAIS 4; the Continuous Performance Test (third edition, CPT3).
Multi-domain cognitive performances assessed by standardized scales as follows [Within 3 Months after inclusion]
- Executive function: The categorical and literal fluency test and the Trail-Making Test (TMT).
Multi-domain cognitive performances assessed by standardized scales as follows [Within 3 Months after inclusion]
- Social cognition: MINI-SEA)
Multi-domain cognitive performances assessed by standardized scales as follows [Within 3 Months after inclusion]
- Depression: CES-D
Multi-domain cognitive performances assessed by standardized scales as follows [Within 3 Months after inclusion]
- Anxiety: HAM-A
Multi-domain cognitive performances assessed by standardized scales as follows [Within 3 Months after inclusion]
- Fatigue: The Chalder Fatigue Scale
Multi-domain cognitive performances assessed by standardized scales as follows [Within 3 Months after inclusion]
- Sleepiness and the impact of sleep disorders: The Epworth Sleepiness Scale

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female, older than 18 years old, no upper age limit
Adult patients with a severe congenital haemostatic defect
Severe or moderate congenital haemophilia A (or B) defined as <5 IU/dL (<5%) endogenous FVIII (FIX) activity at screening
Severe von Willebrand disease defined as VWF: Act ≤15IU/dL (<15%) at screening
Ability of the participant to provide signed and dated informed consent

Exclusion Criteria:

Contraindication for brain MRI
HIV infection to avoid a bias towards severe multifactorial neurological complications
Other known coagulation disorder(s) in addition to haemophilia or von Willebrand disease
Lack of informed consent