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

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

Study Overview

• Status: Completed
• Conditions: Fabry Disease
• Intervention / Treatment: Other: Functional MRI and fast bound-pool fraction imaging

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Fabry Cohort

Inclusion Criteria:

• Have Fabry Disease
• Must be 18yrs or older

Exclusion Criteria:

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

Unaffected Controls

Inclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

OTHER: Fabry; Must be 18 or older and able to have an MRI.

Other: 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.; Other Names: fmri; FBFI; Neuropsychological assessments

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FBFI MRI using advanced MRI technique	advanced quantitative MRI technique (FBFI) to detect and quantify brain lesion in patients with FD	6 months after enrollment closes
Identify difference between patients with Fabry disease and healthy controls in brain function as measured and quantified by functional MRI	identify altered brain function	6 months after enrollment closes
use FBFI and fMRI to map	together to map altered connectivity in response to brain lesions	6 months after enrollment closes

Collaborators and Investigators

• Sponsor: University of Utah
• Collaborators: Genzyme, a Sanofi Company

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 27, 2020
• Primary Completion (ACTUAL): March 30, 2022
• Study Completion (ACTUAL): March 30, 2022

Study Registration Dates

• First Submitted: September 6, 2018
• First Submitted That Met QC Criteria: September 18, 2018
• First Posted (ACTUAL): September 19, 2018

Study Record Updates

• Last Update Posted (ACTUAL): May 26, 2022
• Last Update Submitted That Met QC Criteria: May 19, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: MRI (Magnetic resonance imaging); fabry; Fabry brain lesions
• 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
• Other Study ID Numbers: Fabry MRI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Aggregate data will be published.

Drug and device information, study documents

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