## Protocol Section
### Identification Module
**NCT ID:** NCT03145779

**Brief Title:** Evaluation of Phenotypic Variability in Fabry Disease

**Official Title:** Evaluation of Phenotypic Variability in Fabry Disease

#### Organization Study ID Info
**ID:** IRB-P00022060
#### Organization
**Class:** OTHER
**Full Name:** Boston Children's Hospital
### Status Module
#### Completion Date
**Date:** 2030-07

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2020-12-03

**Type:** ACTUAL

**Last Update Submit Date:** 2020-12-01

**Overall Status:** WITHDRAWN

#### Primary Completion Date
**Date:** 2030-07

**Type:** ESTIMATED

#### Start Date
**Date:** 2020-07

**Type:** ESTIMATED

**Status Verified Date:** 2020-12

#### Study First Post Date
**Date:** 2017-05-09
**Type:** ACTUAL
**Study First Submit Date:** 2017-05-03
**Study First Submit QC Date:** 2017-05-04
**Why Stopped:** Funding
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Boston Children's Hospital

#### Responsible Party

**Investigator Affiliation:** Boston Children's Hospital

**Investigator Full Name:** Farrah Rajabi

**Investigator Title:** Instructor, Division of Genetics and Genomics

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**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.

### Conditions Module

**Conditions:**

- Fabry Disease

### Design Module

#### Design Info

**Observational Model:** CASE_ONLY

**Time Perspective:** PROSPECTIVE

#### Enrollment Info

**Type:** ACTUAL

**Study Type:** OBSERVATIONAL

### Outcomes Module

#### Primary Outcomes

**Description:** Biomarker for deficiency of alpha-galactosidase A (GLA) activity measured to determine if there are changes over time.

**Measure:** Globotriaosylceramide level, plasma

**Time Frame:** Data will be obtained and studied every 2 years for up to 10 years.

**Description:** Biomarker for deficiency of alpha-galactosidase A (GLA) activity measured to determine if there are changes over time.

**Measure:** Globotriaosylceramide level, urine

**Time Frame:** Data will be obtained and studied every 2 years for up to 10 years.

**Description:** Wechsler Adult Intelligence Scale - Revised (WAIS-R) to assess for any changes in intelligence scale over time.

**Measure:** Intelligence scale assessment

**Time Frame:** Data will be obtained and studied every 2 years for up to 10 years.

**Description:** Single score based on questionnaire about quality of life to assess for any changes in scores over time.

**Measure:** Quality of life questionnaire

**Time Frame:** Data will be obtained and studied every 2 years for up to 10 years.

**Description:** Single score based on testing of digit span backwards test, letter fluency, and category fluency to assess any changes in executive function over time.

**Measure:** Executive functioning test

**Time Frame:** Data will be obtained and studied every 2 years for up to 10 years.

**Description:** Single score based on questionnaire about pain to evaluate progression of pain scores over time.

**Measure:** Pain questionnaire

**Time Frame:** Data will be obtained and studied every 2 years for up to 10 years.

**Description:** Physical exam to evaluate for the development of angiokeratoma lesions and neurological symptoms development over time.

**Measure:** Physical exam

**Time Frame:** Data will be obtained and studied every 2 years for up to 10 years.

#### Secondary Outcomes

**Description:** High-throughput RNA sequencing will be done on plasma and peripheral blood lymphocytes to evaluate for changes over time.

**Measure:** Transcriptome analysis

**Time Frame:** Data will be obtained and studied every 2 years for up to 10 years.

**Description:** Comprehensive metabolite mapping of biochemical pathways to determine any metabolomic pathway changes in Fabry disease patients over time.

**Measure:** Metabolomic analysis

**Time Frame:** Data will be obtained and studied every 2 years for up to 10 years.

**Description:** Optional stool sample will be obtained for microbiome analysis to detect the microbiome progression over time in Fabry disease patients.

**Measure:** Microbiome analysis

**Time Frame:** Data will be obtained and studied every 2 years for up to 10 years.

**Description:** Investigators will analyze sequencing results to determine the ability of whole exome sequencing to detect pathogenic modifiers of the Fabry disease phenotype.

**Measure:** Targeted exome sequencing for evaluation of potential modifiers of Fabry disease phenotype.

**Time Frame:** Data will be obtained one time at initial study visit

### Eligibility Module

**Eligibility Criteria:** 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

**Minimum Age:** 1 Year

**Sampling Method:** NON_PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- CHILD

- ADULT

- OLDER_ADULT

**Study Population:** Patients with a diagnosis of Fabry disease.

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Boston

**Country:** United States

**Facility:** Boston Children's Hospital

**State:** Massachusetts

**Zip:** 02115

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000013106

- Term: Sphingolipidoses

- ID: D000020140

- Term: Lysosomal Storage Diseases, Nervous System

- ID: D000020739

- Term: Brain Diseases, Metabolic, Inborn

- ID: D000001928

- Term: Brain Diseases, Metabolic

- ID: D000001927

- Term: Brain Diseases

- ID: D000002493

- Term: Central Nervous System Diseases

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000059345

- Term: Cerebral Small Vessel Diseases

- ID: D000002561

- Term: Cerebrovascular Disorders

- ID: D000014652

- Term: Vascular Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

- ID: D000040181

- Term: Genetic Diseases, X-Linked

- ID: D000030342

- Term: Genetic Diseases, Inborn

- ID: D000008661

- Term: Metabolism, Inborn Errors

- ID: D000008064

- Term: Lipidoses

- ID: D000008052

- Term: Lipid Metabolism, Inborn Errors

- ID: D000016464

- Term: Lysosomal Storage Diseases

- ID: D000008659

- Term: Metabolic Diseases

- ID: D000052439

- Term: Lipid Metabolism Disorders

### Condition Browse Module - Browse Branches

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: BC16

- Name: Diseases and Abnormalities at or Before Birth

- Abbrev: BC18

- Name: Nutritional and Metabolic Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M4124

- Name: Fabry Disease

- Relevance: HIGH

- As Found: Fabry Disease

- ID: M15904

- Name: Sphingolipidoses

- Relevance: LOW

- As Found: Unknown

- ID: M18871

- Name: Lysosomal Storage Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5204

- Name: Brain Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5205

- Name: Brain Diseases, Metabolic

- Relevance: LOW

- As Found: Unknown

- ID: M22498

- Name: Brain Diseases, Metabolic, Inborn

- Relevance: LOW

- As Found: Unknown

- ID: M5742

- Name: Central Nervous System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M29437

- Name: Cerebral Small Vessel Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5810

- Name: Cerebrovascular Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M17400

- Name: Vascular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M24877

- Name: Genetic Diseases, X-Linked

- Relevance: LOW

- As Found: Unknown

- ID: M23686

- Name: Genetic Diseases, Inborn

- Relevance: LOW

- As Found: Unknown

- ID: M11641

- Name: Metabolism, Inborn Errors

- Relevance: LOW

- As Found: Unknown

- ID: M11064

- Name: Lipidoses

- Relevance: LOW

- As Found: Unknown

- ID: M11054

- Name: Lipid Metabolism, Inborn Errors

- Relevance: LOW

- As Found: Unknown

- ID: M11639

- Name: Metabolic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M27029

- Name: Lipid Metabolism Disorders

- Relevance: LOW

- As Found: Unknown

- ID: T2169

- Name: Fabry Disease

- Relevance: HIGH

- As Found: Fabry Disease

- ID: T5335

- Name: Sphingolipidosis

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000000795

- Term: Fabry Disease

### Misc Info Module

- Version Holder: 2024-05-24
