Characterizing the Retinal Microvasculature in Patients with Fabry Disease: a Prospective Observational Study
NCT ID: NCT06758648
Last Updated: 2025-01-06
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
63 participants
OBSERVATIONAL
2020-06-25
2025-11-01
Brief Summary
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The main questions addressed are: Do dynamic and static retinal vessel analysis parameters differ from those in healthy individuals? Can these parameters predict cardiovascular and/or Fabry-related events during follow-up? Do these parameters change during follow-up in patients with a non-stable disease?
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Detailed Description
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Early diagnosis and adequate monitoring of enzyme replacement therapy (ERT) are crucial in reducing the risk of cardiovascular events associated with Fabry disease. Currently, LysoGb3 (lysosphingolipid globotriaosylceramide) is considered a biomarker for the diagnosis and monitoring of Fabry disease. Elevated levels of LysoGb3 have been observed in the blood of patients with Fabry disease, and its measurement has been proposed as a diagnostic tool. Additionally, measuring LysoGb3 levels before and after treatment with ERT can be used as a tool to monitor the effectiveness of the therapy in reducing the accumulation of glycosphingolipids in cells and improving symptoms and outcomes in patients with Fabry disease.
However, the performance of LysoGb3 as a predictor of cardiovascular events in patients with Fabry disease is not well understood, and more research is needed to confirm its utility in this regard.
Therefore, there is a need for additional reliable measurements of the microcirculation that can be performed non-invasively and represent a low burden for participants. The use of non-invasive markers of microcirculation can aid in the early diagnosis and monitoring of Fabry disease, which is crucial for the effective use of ERT.
In summary, this study aims to validate new microcirculation markers that can be measured non-invasively in a prospective cohort of patients with Fabry disease and to correlate these markers with established clinical and laboratory parameters. By validating these markers, the study seeks to improve the management of Fabry disease, reduce the burden on participants, and ultimately reduce the incidence of cardiovascular events associated with the disease.
Conditions
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Study Design
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CASE_CONTROL
PROSPECTIVE
Interventions
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Dynamic retinal vessel analysis (DVA)
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 phenotyping
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)
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 MRI
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)
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.
Echocardiography
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 analysis
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 measurement
Blood pressure measurement to asses cardiovascular risk.
1 hour ECG
One hour ECG to asses autonomic dysfunction in patients with Fabry disease.
Ophthalmological consultation
Evaluation and monitoring of ocular manifestations of Fabry disease.
Static retinal vessel analysis (SVA)
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.
Eligibility Criteria
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Inclusion Criteria
* Diagnosis of Fabry disease by genetic testing or GB3 activity in leukocytes.
* Signed informed consent form
Exclusion Criteria
* Surgery less than 2 weeks prior to inclusion in the study
* Known glaucoma
* Lack of capacity to give consent; lack of informed consent.
* Known epilepsy
18 Years
ALL
No
Sponsors
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Takeda
INDUSTRY
Technical University of Munich
OTHER
Responsible Party
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PD Dr. Christoph Schmaderer
Principal Investigator
Principal Investigators
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Roman Günthner, PD Dr.
Role: PRINCIPAL_INVESTIGATOR
Abteilung für Nephrologie
Timon Kuchler
Role: PRINCIPAL_INVESTIGATOR
Abteilung für Nephrologie
Matthias Braunisch, Pd Dr.
Role: PRINCIPAL_INVESTIGATOR
Abteilung für Nephrologie
Claudia Regenbogen
Role: STUDY_CHAIR
Abteilung für Nephrologie
Christoph Schmaderer
Role: STUDY_DIRECTOR
Abteilung für Nephrologie
Locations
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Department of nephrology, Klinikum rechts der Isar
München, Bavaria, Germany
Countries
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Central Contacts
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Facility Contacts
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Christoph Schmaderer, Prof.Dr.
Role: backup
Matthias Braunisch, PD. Dr.
Role: backup
Roman Günthner, Dr.
Role: backup
Timon Kuchler, Dr
Role: backup
References
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Giannini EH, Mehta AB, Hilz MJ, Beck M, Bichet DG, Brady RO, West M, Germain DP, Wanner C, Waldek S, Clarke JT, Mengel E, Strotmann JM, Warnock DG, Linhart A. A validated disease severity scoring system for Fabry disease. Mol Genet Metab. 2010 Mar;99(3):283-90. doi: 10.1016/j.ymgme.2009.10.178. Epub 2009 Oct 30.
Hughes DA, Bichet DG, Giugliani R, Hopkin RJ, Krusinska E, Nicholls K, Olivotto I, Feldt-Rasmussen U, Sakai N, Skuban N, Sunder-Plassmann G, Torra R, Wilcox WR. Long-term multisystemic efficacy of migalastat on Fabry-associated clinical events, including renal, cardiac and cerebrovascular outcomes. J Med Genet. 2023 Jul;60(7):722-731. doi: 10.1136/jmg-2022-108669. Epub 2022 Dec 21.
Other Identifiers
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FD062020
Identifier Type: -
Identifier Source: org_study_id
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