Clinical trial NCT04639999: Impact of MIgalastat TheRApy on CaRdiac Function in patiEnts With Fabry's Cardiomyopathy (MIRACRE-Fabry Trial)
Official title: Impact of MIgalastat TheRApy on CaRdiac Function in patiEnts With Fabry's Cardiomyopathy (MIRACRE-Fabry Trial)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Fabry Disease
Lead sponsor: Yonsei University
Sponsor class: OTHER
First posted: 2020-11-23
Enrollment: 20
Sex: ALL
Minimum age (years): 16
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients aged 16 \~ 70 years with Fabry disease confirmed by enzyme assay and gene test

Brief summary: This is an observational study. No treatment or intervention will be assigned to the subjects. All patients will receive full standard of care concomitant medication for the treatment of their cardiac condition. 20 patients with genetically confirmed Anderson-Fabry disease who have a plan to start Migalastat will undergo 2D strain, diastolic stress echocardiography, LV vortex flow analysis, and CMR at baseline and after 2 year of treatment with Migalastat for follow-up.

Detailed description: 1. Objectives - to evaluate the impact of chaperone therapy on LV diastolic function and flow in patients with Fabry's cardiomyopathy using LV 2D strain, diastolic stress echocardiography, LV vortex flow and CMR.
2. Primary/Secondary Endpoint

   A. Primary endpoint:

   - Change of peak exercise E/E' by diastolic stress echocardiography, global longitudinal strain and LV vortex flow parameters at 2 year follow up.

   B. Secondary endpoints:
   * Changes of extracellular volume by CMR (T1 mapping) at 2 year follow up
   * Evaluation of the degree of the resting LV diastolic function
   * Evaluation of global and regional LV strain
   * Other echo-parameters; LV mass index at baseline, 2 year follow up, reduction of peak exercise E/E prime at 2 year follow up
   * Changes of quality of life using questionnaire
   * Change of peak VO2, exercise time, AT by diastolic stress echocardiography at 2 year follow up
   * Change in T1 baseline (myo, ms) \& T1 baseline (blood, ms) T1 postcontrast (myo, ms) \& T1 baseline (blood, ms) by CMR
3. Study Methods -Study Design: This is an observational study. No treatment or intervention will be assigned to the subjects. All patients will receive full standard of care concomitant medication for the treatment of their cardiac condition. 20 patients with genetically confirmed Anderson-Fabry disease who have a plan to start Migalastat will undergo 2D strain, diastolic stress echocardiography, LV vortex flow analysis, and CMR at baseline and after 2 year of treatment with Migalastat for follow-up.

Eligibility criteria: Inclusion Criteria:

1. Patients aged 16 \~ 70 years with Fabry's disease who were confirmed by enzyme assay and gene study
2. Patients who have LV hypertrophy in 2D echocardiography (end diastolic septum and posterior wall thickness ≥12mm) or Patients who present with cardiac changes (indicative of disease progression such as decreased global longitudinal strain on 2D strain echocardiography or low native T1 mapping on cardiac MRI) even without LV wall thickness of ≥12mm
3. Patients provided with the written, informed consent to participate in this study

Exclusion Criteria:

1. Contraindication for chaperone therapy (Migalastat)
2. Patients who cannot perform supine bicycle stress echocardiography, contrast echocardiography or cardiac MRI
3. Hemodynamically significant valvular heart disease or arrythmias
4. History of acute myocardial infarction or congestive heart failure with reduced LV ejection fraction of less than 35%
5. CVA in the prior 6 months
6. Scheduled or planned surgery in the next 6 months
7. Chronic liver cirrhosis
8. Allergy to contrast agent (Definity®, Lantheus Medical Imaging, North Billerica, MA, USA)

Primary outcomes:
measure: Change of peak exercise E/E' by diastolic stress echocardiography
timeFrame: 2 years
measure: Change of global longitudinal strain
timeFrame: 2 years
measure: Change of LV vortex flow parameters
timeFrame: 2 years
Secondary outcomes:
measure: Changes of extracellular volume by CMR (T1 mapping)
timeFrame: 2 years
measure: Evaluation of the degree of the resting LV diastolic function
timeFrame: 2 years
measure: Evaluation of global and regional LV strain
timeFrame: 2 years
measure: Evaluation of LV mass index
timeFrame: 2 years
measure: Evaluation of reduction of peak exercise E/E prime
timeFrame: 2 years
measure: Changes of quality of life using Short Form 36
timeFrame: 2 years
measure: Change of peak VO2 by diastolic stress echocardiography
timeFrame: 2 years
measure: Change of exercise time by diastolic stress echocardiography
timeFrame: 2 years
measure: Change of AT by diastolic stress echocardiography
timeFrame: 2 years
measure: Change in T1 baseline (myo, ms) & T1 baseline (blood, ms) T1 postcontrast (myo, ms) & T1 baseline (blood, ms) by CMR
timeFrame: 2 years
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Severance hospital
Study officials:
affiliation: Severance Hospital
name: Geu-Ru Hong, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: