Pulsatility Index, Vasomotor Reactivity and Leukoencephalopathy in Fabry Patients

Association of the Pulsatility Index and Vasomotor Reactivity With White Matter Lesions in Brain MRI of Fabry Disease Patients

We hypothesize that Fabry disease - FD is associated with elevated vascular resistance induced by cerebral small-vessel disease, indicating increased distal resistance to blood flow. The findings of this study may be used as a precursor for neuroimaging manifestations related to stroke in FD patients.

Study Overview

• Status: Completed
• Conditions: Fabry Disease
• Intervention / Treatment: Diagnostic test: Transcranial Doppler (TCD) and Transcranial Color-Coded Duplex (TCCD) ultrasonography

• Study Type: Observational
• Enrollment (Actual): 45

Contacts and Locations

Study Locations

• Greece
  • Athens, Greece, 12462
    • Second Department of Neurology, "Attikon" University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Consecutive patients with genetically confirmed FD and healthy individuals will be prospectively enrolled as part of routine clinical examination.

Description

Inclusion Criteria:

Fabry disease diagnosis, genetically confirmed Age> 16 years

Exclusion Criteria:

Insufficient temporal bone window MRI contra-indication Inability to cooperate for breath-holding test Detection of atrial fibrillation Refuse to sing informed consent

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Fabry disease	Diagnostic test: Transcranial Doppler (TCD) and Transcranial Color-Coded Duplex (TCCD) ultrasonography; Transcranial Doppler (TCD) and Transcranial Color-Coded Duplex (TCCD) ultrasonography will be performed in consecutive FD patients. All TCD and TCCD studies will be performed by stroke neurologists experienced in vascular sonography.
Healthy; age and sex matched	Diagnostic test: Transcranial Doppler (TCD) and Transcranial Color-Coded Duplex (TCCD) ultrasonography; Transcranial Doppler (TCD) and Transcranial Color-Coded Duplex (TCCD) ultrasonography will be performed in consecutive FD patients. All TCD and TCCD studies will be performed by stroke neurologists experienced in vascular sonography.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of elevated pulsatility index of FD patients	to assess the prevalence of elevated pulsatility index in FD patients at a single time point.	2 years
Prevalence of elevated vasomotor reactivity in FD patients.	to assess the prevalence of elevated vasomotor reactivity in FD patients at a single time point.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association of pulsalitily index with leukoencephalopathy in FD patients.	To associate the pulsality index measured by TCD and TCCD with the presence of white matter lesions in brain MRI of FD patients.	2 years
Association of vasomotor reactivity with leukoencephalopathy in FD patients.	To associate the vasomotor reactivity measured by TCD and TCCD with the presence of white matter lesions in brain MRI of FD patients.	2 years
Τo compare the pulsatility index measured in FD patients against corresponding prospectively collected data from healthy individuals, stratified by age and sex.	For the secondary outcome, age and sex-matched healthy controls will be consecutively enrolled. After clinical evaluation, healthy controls will present no FD-associated manifestations, hence they will be FD negative. In addition, brain MRI will be performed and subjects with white matter disease and leukoencephalopathy will be excluded. Included controls will be leukoencephalopathy negative. TCD and TCCD evaluation will be performed in healthy controls, in order to measure pulsatility index and compare the results against FD patients.	2 years
Τo compare vasomotor reactivity measured in FD patients against corresponding prospectively collected data from healthy individuals, stratified by age and sex.	For the secondary outcome, age and sex-matched healthy controls will be consecutively enrolled. After clinical evaluation, healthy controls will present no FD-associated manifestations, hence they will be FD negative. In addition, brain MRI will be performed and subjects with white matter disease and leukoencephalopathy will be excluded. Included controls will be leukoencephalopathy negative. TCD and TCCD evaluation will be performed in healthy controls, in order to measure vasomotor reactivity and compare the results against FD patients.	2 years

Collaborators and Investigators

• Sponsor: National and Kapodistrian University of Athens

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2020
• Primary Completion (Actual): July 1, 2022
• Study Completion (Actual): January 20, 2023

Study Registration Dates

• First Submitted: September 29, 2020
• First Submitted That Met QC Criteria: October 3, 2020
• First Posted (Actual): October 6, 2020

Study Record Updates

• Last Update Posted (Actual): November 9, 2023
• Last Update Submitted That Met QC Criteria: November 7, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: transcranial ultrasound; leukoencephalopathy; pulsatility index; vasomotor reactivity
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Cerebral Small Vessel Diseases; Lipidoses; Lipid Metabolism, Inborn Errors; Fabry Disease; Leukoencephalopathies
• Other Study ID Numbers: FD29092020

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No