Evaluation of Phenotypic Variability in Fabry Disease

Cerebrovascular events, such as stroke, are a devastating complication of Fabry disease that results in part from storage of complex lipids in both large and small vessels. Understanding how the genotype influences the phenotype or clinical presentation can help us understand which patients are at risk for the complications of Fabry disease. This study aims to follow the natural history of this disease will help us understand and predict long-term outcomes for patients.

Study Overview

• Status: Withdrawn
• Conditions: Fabry Disease

Detailed Description

This longitudinal study will be conducted at Boston Children's Hospital (BCH). Subjects recruited for the study will have routine clinical care assessment with a complete physical and neurological exam and biochemical monitoring with venipuncture. In addition as part of the study, subjects will be given questionnaires to assess details of medical and psychosocial history, will complete self-reported measures of neuropsychological evaluation, pain scores, quality of life, executive functioning and cognitive functioning. All patients assessments will be repeated every 2 years.

• Study Type: Observational

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with a diagnosis of Fabry disease.

Description

Inclusion Criteria:

• Individuals who carry a classic alpha-galactosidase gene (GLA) mutation
• All ages
• Medical records available including previous genetic testing.
• Capable of providing informed consent with assent for patients less than 18 years
• Not currently involved in any other clinical trials.

Exclusion Criteria:

• No medical records available
• No record of genotype
• Not capable of providing informed consent
• Currently involved in any clinical trial

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Globotriaosylceramide level, plasma	Biomarker for deficiency of alpha-galactosidase A (GLA) activity measured to determine if there are changes over time.	Data will be obtained and studied every 2 years for up to 10 years.
Globotriaosylceramide level, urine	Biomarker for deficiency of alpha-galactosidase A (GLA) activity measured to determine if there are changes over time.	Data will be obtained and studied every 2 years for up to 10 years.
Intelligence scale assessment	Wechsler Adult Intelligence Scale - Revised (WAIS-R) to assess for any changes in intelligence scale over time.	Data will be obtained and studied every 2 years for up to 10 years.
Quality of life questionnaire	Single score based on questionnaire about quality of life to assess for any changes in scores over time.	Data will be obtained and studied every 2 years for up to 10 years.
Executive functioning test	Single score based on testing of digit span backwards test, letter fluency, and category fluency to assess any changes in executive function over time.	Data will be obtained and studied every 2 years for up to 10 years.
Pain questionnaire	Single score based on questionnaire about pain to evaluate progression of pain scores over time.	Data will be obtained and studied every 2 years for up to 10 years.
Physical exam	Physical exam to evaluate for the development of angiokeratoma lesions and neurological symptoms development over time.	Data will be obtained and studied every 2 years for up to 10 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transcriptome analysis	High-throughput RNA sequencing will be done on plasma and peripheral blood lymphocytes to evaluate for changes over time.	Data will be obtained and studied every 2 years for up to 10 years.
Metabolomic analysis	Comprehensive metabolite mapping of biochemical pathways to determine any metabolomic pathway changes in Fabry disease patients over time.	Data will be obtained and studied every 2 years for up to 10 years.
Microbiome analysis	Optional stool sample will be obtained for microbiome analysis to detect the microbiome progression over time in Fabry disease patients.	Data will be obtained and studied every 2 years for up to 10 years.
Targeted exome sequencing for evaluation of potential modifiers of Fabry disease phenotype.	Investigators will analyze sequencing results to determine the ability of whole exome sequencing to detect pathogenic modifiers of the Fabry disease phenotype.	Data will be obtained one time at initial study visit

Collaborators and Investigators

• Sponsor: Boston Children's Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2020
• Primary Completion (Anticipated): July 1, 2030
• Study Completion (Anticipated): July 1, 2030

Study Registration Dates

• First Submitted: May 3, 2017
• First Submitted That Met QC Criteria: May 4, 2017
• First Posted (Actual): May 9, 2017

Study Record Updates

• Last Update Posted (Actual): December 3, 2020
• Last Update Submitted That Met QC Criteria: December 1, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• 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: IRB-P00022060

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No