Native T1 Mapping by Cardiovascular Magnetic Resonance Imaging in Rare Diseases

NCT ID: NCT03199001

Last Updated: 2017-06-26

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 400 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-02-19
• Study Completion Date: 2019-02-19

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).

Conditions

Fabry Disease

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• Any absolute contraindication to CMR
• Pregnancy

• Minimum Eligible Age: 9 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital Birmingham

OTHER

Sponsor Role: collaborator

University of Sydney

OTHER

Sponsor Role: collaborator

University College, London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Sydney

Sydney, , Australia

Site Status: RECRUITING

University Hospital Birmingham

Birmingham, , United Kingdom

Site Status: RECRUITING

Royal Free Hospital

London, , United Kingdom

Site Status: RECRUITING

The Heart Hospital, University College London Hospital

London, , United Kingdom

Site Status: RECRUITING

Countries

Australia; United Kingdom

Central Contacts

James Moon, MD

Role: CONTACT

j.moon@ucl.ac.uk

Facility Contacts

Rebecca Kozor, PhD

Role: primary

rebeccakozor@gmail.com

Shanat Baig, MRCP

Role: primary

shanat.baig@nhs.net

Sabrina Nordin

Role: primary

sabrina.nordin@nhs.net

Sabrina Nordin, MRCP

Role: primary

sabrina.nordin@nhs.net

References

Sado DM, White SK, Piechnik SK, Banypersad SM, Treibel T, Captur G, Fontana M, Maestrini V, Flett AS, Robson MD, Lachmann RH, Murphy E, Mehta A, Hughes D, Neubauer S, Elliott PM, Moon JC. Identification and assessment of Anderson-Fabry disease by cardiovascular magnetic resonance noncontrast myocardial T1 mapping. Circ Cardiovasc Imaging. 2013 May 1;6(3):392-8. doi: 10.1161/CIRCIMAGING.112.000070. Epub 2013 Apr 5.

Reference Type: BACKGROUND

PMID: 23564562 (View on PubMed)

Pica S, Sado DM, Maestrini V, Fontana M, White SK, Treibel T, Captur G, Anderson S, Piechnik SK, Robson MD, Lachmann RH, Murphy E, Mehta A, Hughes D, Kellman P, Elliott PM, Herrey AS, Moon JC. Reproducibility of native myocardial T1 mapping in the assessment of Fabry disease and its role in early detection of cardiac involvement by cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2014 Dec 5;16(1):99. doi: 10.1186/s12968-014-0099-4.

Reference Type: BACKGROUND

PMID: 25475749 (View on PubMed)

Nappi C, Altiero M, Imbriaco M, Nicolai E, Giudice CA, Aiello M, Diomiaiuti CT, Pisani A, Spinelli L, Cuocolo A. First experience of simultaneous PET/MRI for the early detection of cardiac involvement in patients with Anderson-Fabry disease. Eur J Nucl Med Mol Imaging. 2015 Jun;42(7):1025-31. doi: 10.1007/s00259-015-3036-3. Epub 2015 Mar 26.

Reference Type: BACKGROUND

PMID: 25808629 (View on PubMed)

Vijapurapu R, Nordin S, Baig S, Liu B, Rosmini S, Augusto J, Tchan M, Hughes DA, Geberhiwot T, Moon JC, Steeds RP, Kozor R. Global longitudinal strain, myocardial storage and hypertrophy in Fabry disease. Heart. 2019 Mar;105(6):470-476. doi: 10.1136/heartjnl-2018-313699. Epub 2018 Oct 3.

Reference Type: DERIVED

PMID: 30282640 (View on PubMed)

Other Identifiers

14/0354

Identifier Type: -

Identifier Source: org_study_id