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Establishment of Biomarkers for Fabry Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01165697
Recruitment Status : Completed
First Posted : July 20, 2010
Last Update Posted : January 13, 2017
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
Deb Grzybowski, Ohio State University

Brief Summary:

Fabry disease, an x-linked recessive lysosomal storage disease (LSD) is commonly recognized as a cause of renal failure in involved men and more recently recognized in women too. Women are involved in significant numbers and with complications, as are men, of vascular disease. This manifests as unexpected strokes in young adults. We have morphologic evidence that storage-endotheliopathy induced microvascular disease is the cause of cardiopathy and of cryptogenic strokes, and that storage endotheliopathy starts in early life, probably before birth. Based on our earlier work with other endotheliopathies such as diabetes mellitus, Susac syndrome, and hypertension, we will find and study patients using unique methods, neuro-retinal fluorescein angiography (NRFA), that we have developed for this purpose. These methods include NRFA to demonstrate capillary perfusion in the optic nerve head and retinal quadrants. We anticipate, based on our earlier experience with other endotheliopathies, that we will show more vascular pathology earlier than previously reported. Using epidemiologic and genetic tools we will find more patients than previously known or expected. It will offer opportunity for earlier diagnosis, prognosis, and response to enzyme replacement therapy.

We hypothesize that Fabry disease is a poorly recognized and poorly characterized cause of microvascular disease and cryptogenic strokes in young women and men. Neuroretinal capillary perfusion abnormalities in Fabry disease will be predictive of equivalent vascular disease in kidney, heart, brain and other organs, and further that it will be responsive to change induced by enzyme replacement therapy treatment.

Condition or disease Intervention/treatment
Fabry Disease Other: Fluorescein angiography

Detailed Description:

Specific Aims

Specific Aim 1. To demonstrate the specificity and sensitivity of the diagnostic capabilities of a neuroretinal examination which includes slit lamp and fundoscopy, and NRFA for the diagnosis of Fabry disease on a subject population of identified FD patients.

Specific Aim 2. To show capillary perfusion abnormalities in optic nerve and retina using neuroretinal fluorescein angiography in patients with Fabry disease and compare these to renal (measured by GFR).

Specific Aim 3. To show that the change in capillary perfusion studies when compared to baseline in response to enzyme replacement therapy treatment over time, as a manifestation of tissue burden and prognosis is a more sensitive biomarker of the extent of patient disease than corneal keratopathy.

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Study Type : Observational
Actual Enrollment : 4 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Establishment of Biomarkers for Fabry Disease
Study Start Date : July 2010
Actual Primary Completion Date : July 2014
Actual Study Completion Date : December 2014

Group/Cohort Intervention/treatment
Fabry disease biomarker
Neuro-retinal fluorescein angiography (NRFA) exam will be administered once every 6 months for up to 3 years.
Other: Fluorescein angiography
Fluorescein angiography once every 6 months for 3 years

Primary Outcome Measures :
  1. Presence of specific findings commonly associated with Fabry's disease using neuroretinal examination [ Time Frame: every 6 months, for up to 3 years ]

Secondary Outcome Measures :
  1. Capillary perfusion abnormalities in optic nerve and retina [ Time Frame: every 6 months, for up to 3 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Initially any Fabry patient, age 18 and above who has a confirmed diagnosis of Fabry disease by previously identifying plasma or leukocyte α-galactosidase A (α-gal A) deficiency, will be recruited from all participating physician practices. Those who present with evidence of angiopathy (with specific attention to the target organs: renal, cardiac, or ocular) will be recruited for the study.

Inclusion Criteria:

  • Fabry patient
  • evidence of angiopathy (renal, cardiac, or ocular)
  • Patients above the age of 18

Exclusion Criteria:

  • Patients unable or unwilling to provide written informed consent will not be recruited
  • Patients who are below the age of 18
  • Patients who have not or will not be undergoing Fluorescein angiography
  • Allergy to fluorescein
  • Pregnant women and fetuses are exclude from the study due to risks related to fluorescein and no direct benefit to the pregnant woman and fetus

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01165697

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United States, Ohio
Eye and Ear Institute
Columbus, Ohio, United States, 43212
Sponsors and Collaborators
Ohio State University
Genzyme, a Sanofi Company
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Principal Investigator: Deborah M Grzybowski, PhD Ohio State University


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Responsible Party: Deb Grzybowski, Research Assistant Professor, Ohio State University Identifier: NCT01165697    
Other Study ID Numbers: 2009H0137
First Posted: July 20, 2010    Key Record Dates
Last Update Posted: January 13, 2017
Last Verified: January 2017
Keywords provided by Deb Grzybowski, Ohio State University:
Fabry Disease
vascular disease
storage endotheliopathy
Additional relevant MeSH terms:
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Fabry Disease
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
Cardiovascular Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Metabolism, Inborn Errors
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders