A Study of Migalastat in Fabry Disease

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Fabry Disease

Intervention / Treatment
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* Drug: Migalastat


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed Fabry disease Aged 16 or over Beginning clinical treatment with Migalastat Exclusion Criteria: Contraindication to cardiac MRI

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Migalastat|Participants will be starting Migalastat as part of clinical care. Their initiation onto Migalastat is not determined by this study or it's protocol. Interventions as part of the study will be limited to the study investigations.|

What is the study measuring?
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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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fabry, Anderson-Fabry, Migalastat