Effect of Agalsidase Alfa on Cardiac Inflammation in Patients With Fabry Disease: A [18F]-FDG PET-CMR Study

November 28, 2025 updated by: Yonsei University

Effect of Agalsidase Alfa on Cardiac Inflammation in Patients With Fabry Disease: A [18F]-FDG PET-CMR Study (ESCAPE-FABRY Trial)

This is a prospective observational study. All patients will initiate and maintain treatment with agalsidase alfa during the study period. All patients will receive a full standard of care concomitant medication for the treatment of their cardiac condition. Twenty-five patients with genetically confirmed Anderson-Fabry disease will undergo PET-CMR at baseline and after 12 months of treatment with Agalsidase Alfa for follow-up.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Detailed Description

Visit 1. Screening At screening, for potential eligible patients, after obtaining their informed consent, inclusion/exclusion criteria will be reviewed and enrollment will be determined. Demography (date of birth, gender), prior and concomitant medication and relevant medical history will be recorded. Height, body weight, vital signs, and laboratory assessments will be needed. Women of childbearing potential will be tested for pregnancy.

Visit 2. Baseline Study At visit 2, subjects have following baseline evaluations performed

  • Laboratory test: CBC+PLT, WBC Differential Count, Routine Chemistry (Calcium, Inorganic P, BUN, Creatinine, Fasting Glucose, Cholesterol, Total Protein, Albumin, Total. Bilirubin, Alkaline Phosphatase, AST, ALT), Electrolyte(Na, K, Cl), Lipid profile(Triglyceride, HDL-Cholesterol, LDL-Cholesterol), Plasma Lyso-GB3, NT-proBNP, Troponin T, high-sensitive C-reactive protein, ESR, Interleukin 6, Soluble urokinase plasminogen activator receptor (suPAR), monocyte chemoattractant protein-1(MCP-1), matrix metalloprotease-9(MMP-9), Tumor necrosis factor receptor 2(TNFR2), Urinalysis with Microscopy, Urine test(Microalbumin, Creatinine, Microprotein,Total), Anti-body testing for agalsidase alfa
  • Concomitant medication
  • Vital signs, weight
  • 12-lead ECG
  • QOL questionnaire
  • PET-CMR
  • MIBG cardiac scintigraphy (not mandatory)
  • Conventional Echocardiography including strain imaging

Two-dimensional echocardiography Standard 2-dimensional measurements (LV diastolic and systolic dimensions, ventricular septum and posterior wall thickness, left atrial volume, and LV outflow tract diameter) will be obtained with the patients in the left lateral position. LV ejection fraction (EF) will be calculated by the Simpson's method. From the apical window, a 1- to 2-mm pulsed Doppler sample volume will be placed at the mitral valve tip and mitral flow velocities from 5-10 cardiac cycles will be recorded. Mitral inflow velocities are traced and the following variables will be obtained: peak velocity of early (E) and late (A) filling, and deceleration time of E-wave velocity. Stroke volume (SV) will be measured from LV outflow tract diameter and pulse-wave Doppler signal as previously described. Mitral annular velocity will be measured by Doppler tissue imaging using pulse-wave Doppler mode. The filter will be set to exclude high frequency signal, and the Nyquist limit will be adjusted to a range of 15-20 cm/s. Gain and sample volume will be minimized to allow for a clear tissue signal with minimal background noise. Early diastolic (E') and systolic (S') velocities of the mitral annulus will be measured from the apical 4-chamber view with a 2- to 5-mm sample volume placed at the septal corner of the mitral annulus. All data will be stored digitally and measurements will be taken at the completion of each study. Two-dimensional echocardiographic images from apical views at rest will be acquired, digitized, recorded, and analyzed for the wall motion analysis. Using a dedicated software package (EchoPAC PC), LV-GLS, LV global circumferential strain (LV-GCS), and LV global radial strain (LV-GRS) will be calculated automatically. 2D strain is a non-Doppler-based method for the evaluation of systolic strain using standard 2D acquisitions. LV-GLS strain will be assessed in three apical views, and LV-GCS and LV-GRS will be assessed in three levels of parasternal short-axis views. Left atrial (LA) strain also will be assessed by the same software.

Positron Emission Tomography - Cardiac Magnetic Resonance Imaging (PET-CMR) The PET-CMR procedure will be conducted prior to and within 12 months after initiating Enzyme Replacement Therapy (ERT). All patients are instructed to take a high-fat low-carbohydrate diet the day prior with overnight fast. Administer intravenous unfractionated heparin at a dose of 50 units/kg approximately 15 minutes before the intravenous injection of 10-12 mCi of 18F-FDG. This method is suitable for patients without any bleeding tendencies. After a 90-minute uptake period, cardiac and partial whole body PET images (cerebellum to mid-thigh) are acquired.The F-18 FDG study commences following an oral glucose load of 50 grams, administered one hour prior to injecting 370 MBq of F-18 FDG. A simultaneous cardiac PET/MR study is conducted on an integrated PET/MR scanner (Biograph mMR, Siemens Healthcare, Erlangen, Germany) beginning one hour after the tracer injection. Initially, a standard Dixon sequence is acquired for attenuation correction. Subsequently, comprehensive cardiac MR (CMR) sequences are performed. These include steady-state free precession cine imaging in two-chamber, three-chamber, and four-chamber views, as well as in short-axis images, to ensure detailed cardiac assessment. MR perfusion imaging is performed following gadolinium contrast infusion, and post-contrast late gadolinium enhancement (LGE) studies are executed for detailed tissue characterization. Static F-18 FDG myocardial PET imaging is acquired concurrently during the MRI scans, utilizing list mode for a duration of 30 minutes. The maximal myocardial thickness is noted as 30 mm at end-diastole on cine MRI. The first-pass MR perfusion imaging indicates reduced myocardial blood flow, while patchy F-18 FDG defect areas correspond to regions of LGE, indicative of myocardial fibrosis. Correlate findings from PET and CMR to gain for evaluation of Fabry cardiomyopathy, including assessment of myocardial viability, detection of ischemia, and characterization of tissue.

123I-meta-iodobenzylguanidine scintigraphy The 123I-meta-iodobenzylguanidine (MIBG) scintigraphy will be conducted prior to and within 12 months after initiating ERT. MIBG scintigraphy is expected to provide information to determine whether cardiac sympathetic nerve dysfunction is present in patients with Fabry disease. (8, 9) Because it is reported that decreased MIBG uptake in the inferolateral wall compared with the anteroseptum in patients with LGE of the inferolateral wall in patients with Fabry cardiomyopathy. Moreover, MIBG imaging may play a unique role in assessing the risk of developing ventricular arrhythmia and sudden cardiac death (SCD).

MIBG cardiac imaging will be conducted in according to the current standard.(10, 11) An intravenous dose of 222 MBq 123I-MIBG will be administered by slow (1-2 min) injection through a peripheral venous cannula after thyroid protection via oral intake of 300 mg of potassium perchlorate. All images will be acquired using a Optima NM/CT 640 gamma camera (GE Healthcare, Milwaukee, WI, USA) at 15 (early) and 180 minutes (late) post injection of MIBG. Planar images will be acquired with a low energy high-resolution sensitivity (LEHRS) collimator, 159 keV ± 10% energy window, 256 × 256 image matrix, and zoom of 1.0 (pixel size 2.21 mm) for 1.5 minutes. SPECT images will be acquired over a 180° orbit from the right anterior oblique to left posterior oblique positions with LEHRS collimators, 159 keV ± 10% energy window, 64 × 64 image matrix, zoom of 1.28 (pixel size 6.9 mm) and 60 projections at 17 seconds per projection. The heart-to-mediastinum (H/M) ratio of MIBG uptake and the MIBG defect size will be assessed. MIBG scintigraphy will be conducted for a secondary endpoint and is not mandatory for all patients. It is only performed on patients who have provided consent for the test.

Visit 3. Treatment week 12 At visit 3, subjects have following evaluations performed

  • Concomitant medication
  • Laboratory test: CBC+PLT, WBC Differential Count, Routine Chemistry (Calcium, Inorganic P, BUN, Creatinine, Fasting Glucose, Cholesterol, Total Protein, Albumin, Total. Bilirubin, Alkaline Phosphatase, AST, ALT), Electrolyte(Na, K, Cl), Plasma Lyso-GB3, Urinalysis with Microscopy
  • Vital signs, weight
  • 12-lead ECG
  • QOL questionnaire
  • Adverse events monitoring Visit 4. Treatment week 24 At visit 4, subjects have following evaluations performed
  • Concomitant medication
  • Laboratory test: CBC+PLT, WBC Differential Count, Routine Chemistry (Calcium, Inorganic P, BUN, Creatinine, Fasting Glucose, Cholesterol, Total Protein, Albumin, Total. Bilirubin, Alkaline Phosphatase, AST, ALT), Electrolyte(Na, K, Cl), Plasma Lyso-GB3, NT-proBNP, Troponin T, ESR, Urinalysis with Microscopy
  • Vital signs, weight
  • 12-lead ECG
  • QOL questionnaire
  • Adverse events monitoring

Visit 5. Treatment week 52 (End of study) At visit 5, subjects have following final evaluations performed

  • Laboratory test: CBC+PLT, WBC Differential Count, Routine Chemistry (Calcium, Inorganic P, BUN, Creatinine, Fasting Glucose, Cholesterol, Total Protein, Albumin, Total. Bilirubin, Alkaline Phosphatase, AST, ALT), Electrolyte(Na, K, Cl), Lipid profile(Triglyceride, HDL-Cholesterol, LDL-Cholesterol), Plasma Lyso-GB3, NT-proBNP, Troponin T, high-sensitive C-reactive protein, ESR, Interleukin 6, Soluble urokinase plasminogen activator receptor (suPAR), monocyte chemoattractant protein-1(MCP-1), matrix metalloprotease-9(MMP-9), Tumor necrosis factor receptor 2(TNFR2), Urinalysis with Microscopy, Urine test(Microalbumin, Creatinine, Microprotein,Total), Anti-body testing for agalsidase alfa
  • Concomitant medication
  • Vital signs, weight
  • 12-lead ECG
  • QOL questionnaire
  • PET-CMR
  • MIBG cardiac scintigraphy (not mandatory)
  • Conventional Echocardiography including strain imaging
  • Adverse events monitoring

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
25

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • South Korea
      • Seoul, South Korea, 03722
        • Recruiting
        • Division of Cardiology, Yonsei Cardiovascular Hospital, Yonsei University College of Medicine
        • Contact:
          • Geu-Ru Hong, MD, PhD
          • Phone Number: 82-2-2228-8443
          • Email: GRHONG@yuhs.ac

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients aged 15 ~ 75 years with Fabry disease confirmed by enzyme assay and gene test

Description

Inclusion Criteria:

  • Patients aged 15-75 years with Fabry disease confirmed by enzyme assay and gene test
  • Patients have not undergone ERT for more than 12 months or patients have not used Agalsidase Alfa in the last 12 months.
  • Patients who have cardiac involvement of Fabry disease (end diastolic maximal wall thickness ≥ 12mm on echocardiography or CMR, decreased native T1 value on CMR, unexplained distinct diastolic dysfunction, unexplained decreased global longitudinal strain on 2D strain echocardiography, or biopsy-proven cardiac involvement)
  • Patients provided written informed consent to participate in this study
  • The patient, or patient's legally authorized representative(s), if applicable, understands the nature, scope, and possible consequences of the study and has provided written informed consent that has been approved by the Institutional Review Board/Independent Ethics Committee
  • The patient must be sufficiently cooperative to participate in this clinical study as judged by the investigator.

Exclusion Criteria:

  • Contraindication for enzyme replacement treatment with Agalsidase Alfa
  • Patients have previously been treated with Agalsidase Alfa for > 12 months
  • Patients unable to undergo PET-CMR due to any condition
  • Patients who are pregnant
  • Patients who have active malignancy
  • Subject who the investigator deems inappropriate to participate in this study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Fabry's disease
atients aged 15-75 years with Fabry disease confirmed by enzyme assay and gene test

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
To evaluate the impact of ERT with Agalsidase Alfa on change of myocardial inflammation in patients with Fabry's cardiomyopathy using PET-CMR.
Time Frame: 1 year
To evaluate the impact of ERT with Agalsidase Alfa on change of myocardial inflammation in patients with Fabry's cardiomyopathy using PET-CMR.
1 year

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
To evaluate myocardial inflammation in patients with Fabry disease before ERT
Time Frame: 1 year
To evaluate myocardial inflammation in patients with Fabry disease before ERT
1 year
To evaluate myocardial inflammation in patients with Fabry disease during ERT
Time Frame: 1 year
To evaluate myocardial inflammation in patients with Fabry disease during ERT
1 year
To evaluate myocardial fibrosis in patients with Fabry disease before ERT
Time Frame: 1 year
To evaluate myocardial fibrosis in patients with Fabry disease before ERT
1 year
To evaluate myocardial fibrosis in patients with Fabry disease during ERT
Time Frame: 1 year
To evaluate myocardial fibrosis in patients with Fabry disease during ERT
1 year
To evaluate cardiac cardiac sympathetic nerve dysfunction during ERT
Time Frame: 1 year
To evaluate cardiac cardiac sympathetic nerve dysfunction during ERT
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Yonsei University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 12, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 14, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 14, 2025

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 19, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 1, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 28, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 4-2025-1005

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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