A Study of Migalastat in Fabry Disease (GALAFAB)

A Prospective Observational Study Investigating the Impact of Migalastat on Cardiovascular Structure and Function in Fabry Disease

Fabry disease is a rare metabolic condition characterised by the widespread deposition of sphingolipids in multiple organ systems. Cardiac involvement is common, it occurs in fifty percent of patients and it is the leading cause of death. Despite this, heart and blood vessel (cardiovascular system) manifestations of Fabry disease remain poorly characterised, and it remains unclear which patients benefit from therapy, or when therapy should be initiated. Migalastat is increasingly used to treat fabry disease however the impact of Migalastat on the cardiovascular system is poorly understood. Detailed assessment of the impact of Migalastat on heart and blood vessel structure and function is urgently needed. This observational study will use state of the art, non-invasive investigations to provide greater understanding of the cardiovascular manifestations of Fabry disease and the effects of Migalastat. It will provide insight into which patients respond more effectively to Migalastat, which in turn will facilitate personalisation of therapy, optimisation of the timing of therapy initiation and more cost-effective care.

Study Overview

• Status: Active, not recruiting
• Conditions: Fabry Disease
• Intervention / Treatment: Drug: Migalastat

Detailed Description

This is a prospective longitudinal observational study of patients starting Migalastat as part of routine care. Participants will be recruited from outpatient clinics and have a number of investigations before starting therapy and after twelve months of therapy.

Investigations will include a detailed assessment of symptoms and clinical features, blood tests, echocardiography, detailed cardiac MRI scans, heart rhythm monitoring and exercise capacity assessment.

Parameters will be assessed at baseline and at twelve months.

• Study Type: Observational
• Enrollment (Actual): 21

Contacts and Locations

Study Locations

• United Kingdom
  • Manchester, United Kingdom, M6 8HD
    • Salford Royal NHS Foundation Trust
  • Manchester, United Kingdom, M139LT
    • Manchester University Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients with Fabry disease commencing Migalastat as part of routine care.

Description

Inclusion Criteria:

Confirmed Fabry disease Aged 16 or over Beginning clinical treatment with Migalastat

Exclusion Criteria:

Contraindication to cardiac MRI

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Indexed Left Ventricular Mass (grams/m2)	LV mass, indexed to body surface area, assessed using cardiac MRI.	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in BSA-indexed LV volumes measured using cardiac MRI, from baseline to 12 months (mls/m2)	12 months
Change LV ejection fraction, measured using cardiac MRI (%)	12 months
Change in myocardial extracellular volume, measured using cardiac MRI (%)	12 months
Change in myocardial tissue T1 and T2 times measured using cardiac MRI (ms)	12 months
Change in pulmonary artery systolic pressure, measured using echocardiography (mmHg)	12 months
Change in myocardial PCr/ATP ratio, measured using cardiac MRI spectroscopy (ratio)	12 months
Change in the number of extra heart beats in a 24 hour period, measured using ambulatory heart monitoring. (number)	12 months
Change in exercise capacity - Six minute walk test (meters)	12 months
20. Change in health status (quality of life), measured using change in SF-36 score. (score)	12 months
Change in Lyso-GB3 blood test levels (nmol/L)	12 months
Change in Troponin blood test levels (ng/L)	12 months
Change in NT pro BNP blood test levels (pg/L)	12 months

Collaborators and Investigators

• Sponsor: Manchester University NHS Foundation Trust
• Collaborators: Northern Care Alliance NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2019
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): December 31, 2023

Study Registration Dates

• First Submitted: April 18, 2019
• First Submitted That Met QC Criteria: May 13, 2019
• First Posted (Actual): May 14, 2019

Study Record Updates

• Last Update Posted (Actual): May 31, 2023
• Last Update Submitted That Met QC Criteria: May 30, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Fabry; Migalastat; Anderson-Fabry
• 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: B00544; 19/NW/0099 (Other Identifier: REC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to share IPD with other researchers.

Drug and device information, study documents

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