Pre-Clinical White Matter Changes and Associated Connectivity Effects in Fabry Disease

NCT ID: NCT03678324

Last Updated: 2022-05-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-27
• Study Completion Date: 2022-03-30

Brief Summary

The purpose of this research project is:

• to use an advanced quantitative MRI technique (FBFI) to detect and quantify brain lesion in patients with FD
• to use fMRI to identify altered brain function
• to use FBFI and fMRI together to map altered connectivity in response to brain lesions

Detailed Description

Fabry disease (FD) is a lysosomal storage disease caused by a deficiency in an enzyme that degrades components of the outer cell wall. A deficiency of this enzyme in humans has been associated with stroke. In males with FD, 6.9% have a stroke by 39 years of age. In females with FD, 4.3% have a stroke by 46 years of age.

Magnetic resonance imaging (MRI) is the main tool for studying stroke in FD. Importantly, MRI has identified other types of lesions in the brain beyond that caused by stroke. These additional lesions may herald stroke or be a different manifestation of FD in the brain. These lesions are seen in >50% of men and women with FD.

Diffusion-based imaging MRI has been the leading approach for studying these lesions in FD. However, these lesions that appear to be specific to FD are difficult to quantify, analyze, and interpret using this and other current MRI methods. The Investigators would like to use a form of MRI called fast bound-pool fraction imaging (FBFI), which is a technique better suited to capture and quantify these lesions, to study these lesions in patients with FD. In parallel, the investigators would like to use functional MRI (fMRI) to study how these lesions alter brain function and connectivity in FD. The combination of these techniques (FBFI + fMRI) will also provide us the opportunity to study brain plasticity in response to injury as Fabry disease is slowly progressive over decades allowing the brain to remodel connections to maintain function.

Conditions

Fabry Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Fabry

Must be 18 or older and able to have an MRI.

Group Type: OTHER

Functional MRI and fast bound-pool fraction imaging

Intervention Type: OTHER

Use a form of MRI called fast bound-pool fraction imaging (FBFI), which is a technique better suited to capture and quantify these lesions, to study these lesions in patients with FD. In parallel, we would like to use functional MRI (fMRI) to study how these lesions alter brain function and connectivity in FD.

Neuropsychological assessements will include Wechsler Adult Intelligence Scale, WAIS-III (Digit Span, Symbol-Digit/Coding, and Symbol Search), the Connors Continous Performance text (CPT-II). The Health Questionnaire form, the Center for Epidemiologic Studies Depression Scale (CES-D), the RAND 36-Item Health Survey.

Interventions

Functional MRI and fast bound-pool fraction imaging

Use a form of MRI called fast bound-pool fraction imaging (FBFI), which is a technique better suited to capture and quantify these lesions, to study these lesions in patients with FD. In parallel, we would like to use functional MRI (fMRI) to study how these lesions alter brain function and connectivity in FD.

Neuropsychological assessements will include Wechsler Adult Intelligence Scale, WAIS-III (Digit Span, Symbol-Digit/Coding, and Symbol Search), the Connors Continous Performance text (CPT-II). The Health Questionnaire form, the Center for Epidemiologic Studies Depression Scale (CES-D), the RAND 36-Item Health Survey.

Intervention Type: OTHER

Other Intervention Names

fmri; FBFI; Neuropsychological assessments

Eligibility Criteria

Inclusion Criteria

• Have Fabry Disease
• Must be 18yrs or older

• Must be 18yrs or older
• unaffected with Fabry Disease
• considered healthy with no previous history of stroke, multiple sclerosis, diabetes mellitus, or other neurologic disease.

Exclusion Criteria

• Subjects who are claustrophobic
• have metal implants
• Cannot pass the MRI safety screening questionnaire.

Unaffected Controls

• Subjects who are claustrophobic
• have metal implants
• Cannot pass the MRI safety screening questionnaire.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role: collaborator

University of Utah

OTHER

Sponsor Role: lead

Responsible Party

Hunter Underhill

Assistant Professor of Pediatrics,

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of Utah

Salt Lake City, Utah, United States

Countries

United States

Other Identifiers

Fabry MRI

Identifier Type: -

Identifier Source: org_study_id