A prospective observational study of Migalastat in Fabry disease
Research type
Research Study
Full title
A prospective observational study investigating the impact of Migalastat on cardiovascular structure and function in Fabry Disease
IRAS ID
256995
Contact name
Christopher Miller
Contact email
Sponsor organisation
Manchester University NHS Foundation Trust
Clinicaltrials.gov Identifier
N/A, N/A
Duration of Study in the UK
3 years, 0 months, 0 days
Research summary
Summary of Research
Fabry disease is a rare condition that leads to accumulation of abnormal fatty substances in many organs, including the heart. Heart involvement is common, with 50% of people with Fabry disease developing features of heart disease, and important - heart involvement is the leading cause of death in Fabry disease. 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 (Galafold) is increasingly used to treat fabry disease clinically, 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 heart tests to provide greater understanding of the cardiovascular manifestations of Fabry disease and effect 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.
Summary of Results
Background: Migalastat is a recommended treatment for genetically amenable patients exhibiting cardiovascular manifestations of Fabry disease. Previous studies have shown migalastat is associated with a reduction in left ventricular mass indexed for body surface area (LVMI). The impact of migalastat on other aspects of cardiovascular structure and function, heart rhythm, exercise tolerance and quality of life are unknown.
Objective: To comprehensively evaluate the impact of migalastat on cardiovascular structure and function, heart rhythm, exercise tolerance and quality of life.
Methods: Patients with genetically confirmed Fabry disease beginning treatment with migalastat underwent procedures at baseline and 12-months including: cardiovascular magnetic resonance, 31Phosphorus and 1Hydrogen magnetic resonance spectroscopy, serum and urine biomarker analysis, 6-minute walk testing, cardiopulmonary exercise testing and SF-36 health questionnaire. Two comparator groups were included: 1. Patients established on enzyme replacement therapy; 2. Treatment naïve patients.
Results: Twenty-one patients were included in each group (total 63 patients). Migalastat was not associated with a significant change in LVMI (baseline: median 73.0 (interquartile range 62.3-108.5) g/m2; follow-up: 78.8 (67.3 - 113.9) g/m2; change: 0.47 ± 7.94 g/m2; p=0.388), or most other measurements of cardiovascular structure and function. Migalastat was associated with an increase in six-minute walk test distance (453.0 ± 165.0 to 504.0 ± 160.0 metres; change 29.3 ± 45.0 metres; p=0.037), but not other measurements of exercise capacity.
Conclusions: The initial 12 months of migalastat were not associated with a significant change in LVMI, or most other measurements of cardiovascular structure and function, heart rhythm and quality of life. A possible positive impact on exercise tolerance requires further investigation.REC name
North West - Greater Manchester East Research Ethics Committee
REC reference
19/NW/0099
Date of REC Opinion
15 Apr 2019
REC opinion
Further Information Favourable Opinion