Impact of Agalsidase Alfa Therapy on Cardiac funcTION in Patients With Fabry's Cardiomyopathy

Impact of Agalsidase Alfa Therapy on Cardiac funcTION in Patients With Fabry's Cardiomyopathy (ACTION-Fabry Trial)

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. 25 patients with genetically confirmed Anderson-Fabry disease who have a plan to start ERT with Agalsidase Alfa will undergo 2D strain, diastolic stress echocardiography, LV vortex flow analysis, and CMR at baseline and after 1 year of treatment with ERT with Agalsidase Alfa for follow-up.

Study Overview

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

Detailed Description

1. Objectives - The purpose of this study is to evaluate the impact of ERT with Agalsidase Alfa 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 1) Primary endpoint:

   • Change from baseline in peak exercise E/E' by diastolic stress echocardiography, global longitudinal strain and LV vortex flow parameters at 1 year 2) Secondary endpoints:

   • Changes from baseline in extracellular volume by CMR (T1 mapping) at 1 year follow up

     • Changes from baseline in evaluation of the degree of the resting LV diastolic function

       • Changes from baseline in other echo-parameters; LV mass index, reduction of peak exercise E/E prime at 1 year follow up

         • Changes from baseline in quality of life using questionnaire ⑤ Change from baseline in peak VO2, exercise time, AT by diastolic stress echocardiography at 1 year follow up ⑥ Change in T1 baseline (myo, ms) & T1 baseline (blood, ms), T1 postcontrast (myo, ms) & T1 baseline (blood, ms) by CMR
3. Study Methods 1) 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. 25 patients with genetically confirmed Anderson-Fabry disease who have a plan to start ERT with Agalsidase Alfa will undergo 2D strain, diastolic stress echocardiography, LV vortex flow analysis, and CMR at baseline and after 1 year of treatment with ERT with Agalsidase Alfa for follow-up.

• Study Type: Observational
• Enrollment (Anticipated): 25

Contacts and Locations

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

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Recruiting
    • Division of Cardiology, Yonsei Cardiovascular Hospital, Yonsei University College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients aged 16 ~ 75 years with Fabry disease confirmed by enzyme assay and gene test

Description

Inclusion Criteria:

• Patients aged 16~ 75 years with Fabry disease confirmed by enzyme assay and gene test
• Patients who have LVH 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 CMR)
• Patients provided written informed consent to participate in this study

Exclusion Criteria:

• Contraindication for enzyme replacement treatment with Agalsidase Alfa
• Patients who cannot receive supine bicycle stress echocardiography, contrast echocardiography or CMR
• Patients with hemodynamically significant valvular heart disease or arrhythmias
• Patients who have history of acute myocardial infarction or congestive heart failure with reduced LV ejection fraction of less than 35%
• Patients who had any cerebrovascular accident in the prior 6 months
• Scheduled or planned surgery in the next 6 months
• Patients with chronic liver cirrhosis
• Patients who are allergic to contrast agent (e.g. Definity�, Lantheus Medical Imaging, North Billerica, MA, USA)

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

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	Measure Description	Time Frame
peak exercise E/E' by diastolic stress echocardiography	Change from baseline in peak exercise E/E' by diastolic stress echocardiography	1 year
global longitudinal strain		1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
extracellular volume by CMR	Changes from baseline in extracellular volume by CMR (T1 mapping) at 1 year follow up	1 year
evaluation of the degree of the resting LV diastolic function	Changes from baseline in evaluation of the degree of the resting LV diastolic function	1 year
quality of life using questionnaire	Changes from baseline in quality of life using questionnaire	1 year

Collaborators and Investigators

• Sponsor: Yonsei University

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2017
• Primary Completion (Anticipated): January 1, 2025
• Study Completion (Anticipated): January 1, 2025

Study Registration Dates

• First Submitted: July 21, 2017
• First Submitted That Met QC Criteria: July 23, 2017
• First Posted (Actual): July 26, 2017

Study Record Updates

• Last Update Posted (Actual): June 24, 2021
• Last Update Submitted That Met QC Criteria: June 23, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Cardiomyopathy; Cardiac MRI; Enzyme replacement therapy; Fabry's disease; Agalsidase Alfa; Diastolic stress echocardiography; LV vortex flow
• 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: 4-2017-0471

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