Characterizing the Retinal Microvasculature in Patients with Fabry Disease: a Prospective Observational Study

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

• Ages 18 years and older
• All sexes
• No healthy volunteers
• Adult, Older adult

Study population: Patients included in this study are recruited through our in-house metabolic outpatient clinic (Stoffwechselambulanz), which specializes in the diagnosis, treatment, and long-term management of rare metabolic disorders, including Fabry disease. The clinic serves as a comprehensive care center, offering multidisciplinary services such as genetic counseling, laboratory diagnostics, and individualized treatment planning. Patients are identified and approached during routine follow-ups or initial consultations after confirmation of a Fabry disease diagnosis through genetic testing or measurement of globotriaosylceramide (Gb3) activity in leukocytes. This structured recruitment process ensures the inclusion of well-characterized patients who meet the study's eligibility criteria.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

About this study

Conditions

Fabry Disease, Endothelial Dysfunction, Microvasculature

Being tested

Dynamic retinal vessel analysis (DVA), Biochemistry and immune phenotyping, Questionnaires (Patient reported outcomes), Cardio MRI, Optical coherence tomography (OCT)

Keywords

Chronic inflammation, retinal microvasculature, retinal vessel analysis, vasculopathy

Medical subject headings

Fabry Disease, Vascular Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

• Dynamic retinal vessel analysis (DVA)Diagnostic test

  Dynamic retinal vessel analysis (DVA) is an established, non-invasive technique for evaluating the responsiveness of retinal vessels to flickering light stimuli. This technique allows for the measurement of changes in retinal vessel diameter in response to changes in blood flow, providing insight into the microcirculatory function of the retina. In the case of DVA, patients will asked to focus on a needle, and one arteriole and venule diameter were automatically and continuously recorded. Arteriole and venule segments between 0.5 to 1 mm will be analyzed approximately 2-disc diameters away from the optic nerve in a lower-temporal direction. The baseline recording will be 50 seconds, followed by a flickering phase of 20 seconds and then a recovery period of 80 seconds. Three of these cycles were performed.

  Based on this, we will calculate the percentage of maximum arteriolar (aFID) and venular dilation (vFID) to baseline.

• Biochemistry and immune phenotypingDiagnostic test

  Collection of blood samples from participants for the purpose of performing clinical chemistry analysis. Peripheral blood mononuclear cells (PBMCs) will be isolated from the collected blood samples using standard techniques, such as density gradient centrifugation, and will be analyzed using fluorescence-activated cell sorting (FACS)

• Questionnaires (Patient reported outcomes)Diagnostic test

  This study involves a comprehensive evaluation of life quality, pain, and gastrointestinal (GI) symptoms using a set of established and validated questionnaires. The tools employed include the SF-36 (Short Form-36 Health Survey) to assess overall health-related quality of life across multiple domains, the COMPASS-31 (Composite Autonomic Symptom Score) to evaluate autonomic dysfunction symptoms, and the Brief Pain Inventory (BPI) to measure pain severity and its impact on daily activities. Additionally, the Gastrointestinal Symptom Rating Scale (GSRS) is used to quantify the severity and frequency of GI symptoms, covering dimensions such as reflux, abdominal pain, indigestion, diarrhea, and constipation. Together, these questionnaires provide a multidimensional assessment of the patient's physical, emotional, and symptomatic experiences, allowing for a robust understanding of their health status and quality of life.

• Cardio MRIDiagnostic test

  Cardiovascular magnetic resonance imaging (CMR or cardio MRI) will be utilized in patients with Fabry disease. This imaging technique will enable detailed assessment and monitoring of key cardiac abnormalities, including thickening of the heart walls, left ventricular hypertrophy, and decreased blood flow in the coronary vessels. Additionally, T1 relaxation time measurement will be conducted, offering a non-invasive means to detect myocardial tissue abnormalities such as fibrosis and sphingolipid accumulation, which are hallmarks of Fabry disease. Together, these measures provide a comprehensive evaluation of cardiac structure, function, and tissue characteristics in affected patients.

• Optical coherence tomography (OCT)Diagnostic test

  Optical coherence tomography (OCT) is a non-invasive, high-resolution imaging technique that utilizes low-coherence light to capture cross-sectional images of the ocular fundus. Based on the principle of interferometry, OCT employs low-coherence light, which is scattered by the tissue, to produce detailed, high-resolution images of the retina and its layers. This technology enables precise visualization of the different retinal layers, including the nerve fiber layer, the ganglion cell layer, and the inner and outer plexiform layers. Additionally, OCT can be used to detect and monitor subtle structural changes in the retina, offering critical insights into retinal microarchitecture and potential manifestations of systemic diseases such as Fabry disease.

• EchocardiographyDiagnostic test

  Detection of signs of left ventricular hypertrophy, diastolic dysfunction, and valvular disease, which are common cardiac complications associated with Fabry disease, will be a key focus of the assessment. These abnormalities are indicative of the progressive cardiac involvement characteristic of the disease. Left ventricular hypertrophy reflects the thickening of the heart muscle, often caused by sphingolipid accumulation, while diastolic dysfunction highlights impaired relaxation and filling of the left ventricle. Valvular disease, including regurgitation or stenosis, further contributes to the cardiac burden in Fabry disease. Identifying and monitoring these conditions are essential for timely intervention and effective management of cardiac manifestations in affected patients.

• 24 hour pulse wave analysisDiagnostic test

  Pulse wave analysis (PWA) is a non-invasive method used to assess the cardiovascular system. It uses a sensor to measure the pressure waves generated by the heart's contraction and the subsequent blood flow through the peripheral vessels. By analyzing these pressure waves, PWA can provide information about the elasticity of the arterial walls, the blood flow in the peripheral vessels, the blood pressure, and the arterial stiffness.

• 24-hour blood pressure measurementDiagnostic test

  Blood pressure measurement to asses cardiovascular risk.

• 1 hour ECGDiagnostic test

  One hour ECG to asses autonomic dysfunction in patients with Fabry disease.

• Ophthalmological consultationDiagnostic test

  Evaluation and monitoring of ocular manifestations of Fabry disease.

• Static retinal vessel analysis (SVA)Diagnostic test

  Comparable to DVA, SVA is a non-invasive and quick tool to examine the retinal microvasculature. SVA pictures will be analyzed using Vesselmap 2® (IMEDOS Systems GmbH, Jena, Germany). One eye will be examined, and three images will be taken with a focus on the optic disc at an angle of 50°. Roughly one disc diameter away from the optic disc, retinal veins and arterioles segments will be semi-automatically labeled. The Paar-Hubbard formula averages the central retinal arteriolar (CRAE) and central venular (CRVE) equivalents.

  The arteriolar-venular ratio will be calculated as CRAE/CRVE.

What is being measured

The primary outcome is the main question the study is designed to answer.

1. Change in Retinal Arteriolar Diameter (CRAE)

   What will be measured: Central Retinal Arteriolar Equivalent (CRAE) in micrometers (µm).

   Unit of Measure: Micrometers (µm). How it will be reported: Mean CRAE values at baseline for Fabry disease patients compared with age- and sex-matched healthy controls.

   Measured: From enrollment (T0) to the occurrence of death or the end of the study, whichever comes first, assessed over an estimated period of up to 4 years. Measurements will be conducted annually, starting at T0, then at 1 year (T1), 2 year (T2), T3 and T4.

2. Change in Retinal Arteriolar Diameter (CRVE)

   What will be measured: Central Retinal Arteriolar Equivalent (CRVE) in micrometers (µm).

   Unit of Measure: Micrometers (µm). How it will be reported: Mean CRAE values at baseline for Fabry disease patients compared with age- and sex-matched healthy controls.

   Measured: From enrollment (T0) to the occurrence of death or the end of the study, whichever comes first, assessed over an estimated period of up to 4 years. Measurements will be conducted annually, starting at T0, then at 1 year (T1), 2 year (T2), T3 and T4.

3. Change in arteriolar-venular ration (AVR)

   What will be measured: AVR as a quotient out of CRAE/CRVE Unit of Measure: no unit How it will be reported: Mean or Median AVR values at baseline for Fabry disease patients compared with age- and sex-matched healthy controls.

   Measured: From enrollment (T0) to the occurrence of death or the end of the study, whichever comes first, assessed over an estimated period of up to 4 years. Measurements will be conducted annually, starting at T0, then at 1 year (T1), 2 year (T2), T3 and T4.

4. Change in Flicker-Induced Venular Dilation (vFID)

   What will be measured: Maximum percentage change in retinal venular diameter during flicker stimulation.

   Unit of Measure: Percentage (%). How it will be reported: Mean vFID percentage change at baseline for Fabry disease patients compared with age- and sex-matched healthy controls.

   Measured: From enrollment (T0) to the occurrence of death or the end of the study, whichever comes first, assessed over an estimated period of up to 4 years. Measurements will be conducted annually, starting at T0, then at 1 year (T1), 2 year (T2), T3 and T4

5. Change in Flicker-Induced Venular Dilation (aFID)

   What will be measured: Maximum percentage change in retinal arteriolar diameter during flicker stimulation.

   Unit of Measure: Percentage (%). How it will be reported: Mean vFID percentage change at baseline for Fabry disease patients compared with age- and sex-matched healthy controls.

   Measured: From enrollment (T0) to the occurrence of death or the end of the study, whichever comes first, assessed over an estimated period of up to 4 years. Measurements will be conducted annually, starting at T0, then at 1 year (T1), 2 year (T2), T3 and T4

6. Predictive Value of SVA and DVA Parameters in Fabry Disease Outcomes

   What will be measured: The predictive value of Static Retinal Vessel Analysis (SVA) parameters (CRAE, CRVE, AVR) and Dynamic Retinal Vessel Analysis (DVA) parameters (vFID, aFID) in forecasting Fabry disease-associated events (FACE) FACE are measured as preciously described (https://pmc.ncbi.nlm.nih.gov/articles/PMC10359570/) Unit of Measure: Micrometers (µm) for CRAE, CRVE; unitless ratio for AVR; percentage (%) for vFID and aFID.

   Measurement Tools: Retinal vessel analyzers (Static Retinal Vessel Analyzer and Dynamic Retinal Vessel Analyzer, IMEDOS Systems, Jena, Germany), echocardiography, clinical laboratory markers (e.g., LysoGb3), and DS3 scoring system. FACE.

   How it will be reported Hazard Ratios (HR): Derived from Cox proportional hazard models Odds Ratios (OR): For binary outcomes Multivariable Regression Models

   Receiver Operating Characteristic (ROC) Analysis:

   Correlation Coefficients: (e.g., Pearson or Spearman)

   Measured: From enrollment (T0) to the occurrence of death /FACE or the end of the study, whichever comes first, assessed over an estimated period of up to 4 years. Measurements will be conducted annually, starting at T0, then at 1 year (T1), 2 year (T2), T3 and T4

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1. First posted6 Jan 2025
2. Study start25 Jun 2020
3. Primary completion1 Sep 2021
4. Study completion1 Nov 2025 (estimated)

Resources

• Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
• Publications (3)Papers the sponsor has linked to this study.
• Other trials for Fabry DiseaseStudies of the same condition, open and under way.
• More trials run by Technical University of MunichThe sponsor's other registered studies.
• What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.