the Role of cArdiac Inflammation, endoThelial Dysfunction, and FIbrosis in fabrY Disease

NCT06776419 | Recruiting DMC

• 1 other identifier: H-24052180
• Study Type: observational
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

The overall objective of this study is to investigate Fabry-related cardiomyopathy and the use of native T1-mapping, coronary microvascular function, cardiac inflammation, and cardiac injury in an effort to improve the ability to detect disease. The study aims to achieve this by:

1. 1.Investigating the association between cardiac inflammation, fibrosis, and injury against the distribution and degree of microvascular disease in patients with Fabry disease with and without left ventricular hypertrophy (LVH) using cardiac magnetic resonance (CMR) imaging and 82Rubidium Positron emission tomography and computer tomography (82Rb-PET/CT).
2. 2.Using an extensive, in-depth biomarker blood panel to investigate the pathological pathways associated with Fabry disease and Fabry-related cardiomyopathy.

Conditions

Fabry Disease; Cardiovascular Diseases

Keywords

Hypertrophy; Inflammation; Myocardium; Fibrosis Myocardial; Endothelial dysfunction; Coronary Microcirculation

Outcome Measures

Primary Outcomes (2)

• Change in global myocardial flow reserve

  A between-group difference in change in global myocardial flow reserve (MFR), evaluated by 82Rb-PET/CT, comparing Fabry patients with controls irrespective of the presence of LVH.

  3 year change

• Change in global native T1

  A between-group difference in change in global native T1 evaluated by MRI, comparing Fabry patients with controls irrespective of the presence of LVH.

  3 year change

Secondary Outcomes (4)

• Change in global myocardial flow reserve by group

  3 year change

• Change in global T1 by group

  3 year change

• Change in global T2 by group

  3 year change

• Change in global T2

  3 year change

Other Outcomes (6)

• Change in regional myocardial flow reserve

  3 year change

• Change in regional T1

  3 year change

• Change in regional T2

  3 year change

Study Arms (2)

Patients with Fabry Disease

Patients with a genetically verified diagnosis of Fabry disease, grouped by the presence of left ventricular hypertrophy

Diagnostic Test: Cardiac Magnetic Ressonance Imaging; Diagnostic Test: 82Rubidium-positron emission tomography and computer-tomography

Controls

Healthy age- and sex-matched controls

Diagnostic Test: Cardiac Magnetic Ressonance Imaging; Diagnostic Test: 82Rubidium-positron emission tomography and computer-tomography

Interventions

Cardiac Magnetic Ressonance Imaging DIAGNOSTIC_TEST

CMR-protocol with gadolinium contrast

Also known as: CMR

Controls; Patients with Fabry Disease

82Rubidium-positron emission tomography and computer-tomography DIAGNOSTIC_TEST

cardiac Rb-PET protocol

Also known as: 82Rb-PET/CT

Controls; Patients with Fabry Disease

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

1. Patients (adult) with genetically-verified diagnosis of Fabry disease. 2. Age- and sex-matched healthy controls.

You may qualify if:

• Male and female individuals with a genetically-verified diagnosis of Fabry disease
• ≥ 18 years of age
• Able to give informed consent

You may not qualify if:

• Any contraindication against a pharmacologically induced rest-stress PET/CT protocol according to local safety procedures such as acute coronary syndrome, severe bronchospasm, severe chronic obstructive pulmonary disease, cardiac arrhythmia.
• Any contraindication for MRI according to standard checklist used in clinical routine, including claustrophobia or metallic foreign bodies, metallic implants, internal electrical devices, or permanent makeup/tattoos that cannot be declared MR compatible.
• Pregnancy
• Age and sex-matched healthy controls (2)
• ≥ 18 years of age
• Able to give informed consent
• A genetically-verified diagnosis of Fabry disease.
• Family member to a patient with a genetically-verified diagnosis of Fabry disease
• Cancer expected to influence life expectancy.
• Known heart failure, previous apoplexy or previously established kidney disease.
• Initiation or change of antihypertensive therapy within 3 months of enrollment.
• Known LVH as evaluated on echocardiography
• Any contraindication for a pharmacologically induced stress PET/CT protocol according to local safety procedures such as acute coronary syndrome, severe bronchospasm, severe chronic obstructive pulmonary disease, cardiac arrhythmia.
• Any contraindication for MRI according to standard checklist used in clinical routine, including claustrophobia or metallic foreign bodies, metallic implants, internal electrical devices, or permanent makeup/tattoos that cannot be declared MR compatible.
• Pregnancy

Sponsors & Collaborators

• Caroline Michaela Kistorp: lead
• Sanofi: collaborator

Study Sites (1)

Rigshospitalet

Copenhagen, 2100, Denmark

RECRUITING

Related Publications (27)

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Biospecimen

Retention: SAMPLES WITH DNA

Blood and urine

MeSH Terms

Conditions

Fabry Disease; Cardiovascular Diseases; Hypertrophy; Myocarditis

Condition Hierarchy (Ancestors)

Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Vascular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Cardiomyopathies; Heart Diseases

Study Officials

• Caroline Kistorp, Professor

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Caroline Kistorp, Professor

CONTACT

35459642; caroline.michaela.kistorp@regionh.dk

Niels Høeg Brandt-Jacobsen, PhD, MD

CONTACT

35458177; niels.hoeeg.brandt-jacobsen.01@regionh.dk

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 9, 2025
• First Posted: January 15, 2025
• Study Start: May 1, 2025
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): June 1, 2031
• Last Updated: April 8, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)