Impact of MIgalastat TheRApy on CaRdiac Function in patiEnts With Fabry's Cardiomyopathy (MIRACRE-Fabry Trial)

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.

Study Overview

• Status: Recruiting
• Conditions: Fabry Disease
• Intervention / Treatment: Other: Echocardiography

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.

• Study Type: Observational
• Enrollment (Anticipated): 20

Contacts and Locations

• Study Contact: Name: Geu-Ru Hong, Ph.D; Phone Number: 82+2-2228-8443; Email: grhong@yuhs.ac

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Recruiting
    • Severance Hospital
    • Contact: Geu-Ru Hong, Ph.D; Phone Number: 82+2-2228-8443; Email: grhong@yuhs.ac

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 70 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients aged 16 ~ 70 years with Fabry disease confirmed by enzyme assay and gene test

Description

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)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Fabry's disease; Fabry's disease patients who were confirmed by enzyme assay and gene study	Other: Echocardiography; LV vortex flow in Echocardiography

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change of peak exercise E/E' by diastolic stress echocardiography	2 years
Change of global longitudinal strain	2 years
Change of LV vortex flow parameters	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes of extracellular volume by CMR (T1 mapping)	2 years
Evaluation of the degree of the resting LV diastolic function	2 years
Evaluation of global and regional LV strain	2 years
Evaluation of LV mass index	2 years
Evaluation of reduction of peak exercise E/E prime	2 years
Changes of quality of life using Short Form 36	2 years
Change of peak VO2 by diastolic stress echocardiography	2 years
Change of exercise time by diastolic stress echocardiography	2 years
Change of AT by diastolic stress echocardiography	2 years
Change in T1 baseline (myo, ms) & T1 baseline (blood, ms) T1 postcontrast (myo, ms) & T1 baseline (blood, ms) by CMR	2 years

Collaborators and Investigators

• Sponsor: Yonsei University
• Investigators: Principal Investigator: Geu-Ru Hong, Ph.D, Severance Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 5, 2020
• Primary Completion (ANTICIPATED): January 1, 2025
• Study Completion (ANTICIPATED): April 1, 2025

Study Registration Dates

• First Submitted: November 10, 2020
• First Submitted That Met QC Criteria: November 16, 2020
• First Posted (ACTUAL): November 23, 2020

Study Record Updates

• Last Update Posted (ACTUAL): October 14, 2021
• Last Update Submitted That Met QC Criteria: October 5, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Cerebral Small Vessel Diseases; Lipidoses; Lipid Metabolism, Inborn Errors; Cardiomyopathies; Fabry Disease
• Other Study ID Numbers: 4-2020-1038

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No