Evaluation of Phenotypic Variability in Fabry Disease

Withdrawn

• Conditions: Fabry Disease

• Registration Number: NCT03145779
• Lead Sponsor: Boston Children's Hospital

Brief Summary

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.

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 Timeline

• Study First Submitted: 2017-05-03
• Study First Submitted QC: 2017-05-04
• Study First Posted: 2017-05-09
• Study Start: 2020-07
• Status Verified: 2020-12
• Last Update Submitted: 2020-12-01
• Last Update Posted: 2020-12-03
• Primary Completion: 2030-07
• Study Completion: 2030-07

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Boston Children's Hospital; 🇺🇸 Boston, Massachusetts, United States