Native T1 Mapping by Cardiovascular Magnetic Resonance Imaging in Rare Diseases

• Conditions: Fabry Disease

• Registration Number: NCT03199001
• Lead Sponsor: University College, London

Brief Summary

Fabry Disease (FD) is a rare, X-linked lysosomal storage disorder leading to left ventricular hypertrophy, myocardial fibrosis, arrhythmia and heart failure. Cardiac involvement is the leading cause of death in FD. Treatment with enzyme replacement therapy is expensive, may be poorly targeted and there are difficulties in early detection and disease monitoring. T1 mapping signal change is a potential remarkable biomarker for FD.

Fabry400 is a multicentre study aiming to understand the biology of Fabry Disease and its relationship to non-invasive multi parametric mapping by CMR.

Detailed Description

Our understanding of cardiac involvement in FD is limited because the myocyte storage cannot be assessed non-invasively. However with the development of CMR T1 mapping this maybe possible. T1 mapping demonstrated excellent discrimination between FD and other causes of LVH, and this property is highly suggestive of a direct but intricate relationship between T1 signals and abnormal fat storage. Specifically, 50% of patients without LVH have low T1 values, suggesting that T1 is an early disease marker in FD. This property may prove particularly useful for assessing disease progression and treatment response in early disease.

In CMR, LGE in FD characteristically occurs in the basal inferolateral wall. LGE is associated with a poor response to therapy and adverse outcomes. Hybrid imaging with PET/MR has shown that some FD LGE may be inflammation. T2 mapping may be useful as it is a sensitive detector of inflammation and oedema, for example discriminating acute from chronic myocardial infarction, and diagnosing myocarditis, particularly in the setting of chronic myocarditis or heart failure.

The aims of this study are:

1. Improve the diagnosis of cardiac involvement by recognition of early disease

2. Detect early changes and responses to therapy

3. Improve the understanding of the pathophysiology of cardiac involvement using multiparametric mapping by CMR

Study Method:

This is a cohort observational study of FD patients including children, patients starting ERT, ERT naïve patients and LVH positive patients. Follow up scans at 6 months and 12 months will be done on patients starting ERT. CMR Scanning will use T1 and T2 mapping techniques against established gold-standard sequences. The patients will also have ECHO and ECG. Blood biomarkers will be collected (serum, plasma and urine).

Study Timeline

• Study Start: 2015-02-19
• Status Verified: 2017-06
• Study First Submitted: 2017-06-19
• Study First Submitted QC: 2017-06-23
• Last Update Submitted: 2017-06-23
• Study First Posted: 2017-06-26
• Last Update Posted: 2017-06-26
• Primary Completion: 2018-08-19
• Study Completion: 2019-02-19

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 400

Inclusion Criteria

• Gene-positive Fabry Disease
• Male or female
• Age at least 9 years

Exclusion Criteria

• Any absolute contraindication to CMR
• Pregnancy

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Presence of storage in Fabry cardiomyopathy	1 hour	Presence or absence of storage (measured in milliseconds) by T1 mapping by CMR

Secondary Outcome Measures

Name	Time	Method
Presence of inflammation in Fabry cardiomyopathy	1 hour	Presence or absence of inflammation (measured in milliseconds) by T2 mapping by CMR
Change in storage measure	12 months	Change in storage measure (measured in milliseconds) by T1 mapping by CMR

Trial Locations

Locations (4)

The Heart Hospital, University College London Hospital; 🇬🇧 London, United Kingdom

University Hospital Birmingham; 🇬🇧 Birmingham, United Kingdom

University of Sydney; 🇦🇺 Sydney, Australia

Royal Free Hospital; 🇬🇧 London, United Kingdom