Establishment of Biomarkers for Fabry Disease

January 11, 2017 updated by: Deb Grzybowski, Ohio State University

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Actual)

4

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

  • United States
    • Ohio
      • Columbus, Ohio, United States, 43212
        • Eye and Ear Institute

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

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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.

Description

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

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

  • Observational Models: Case-Only
  • Time Perspectives: Prospective

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Presence of specific findings commonly associated with Fabry's disease using neuroretinal examination
Time Frame: every 6 months, for up to 3 years
every 6 months, for up to 3 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Capillary perfusion abnormalities in optic nerve and retina
Time Frame: every 6 months, for up to 3 years
every 6 months, for up to 3 years

Collaborators and Investigators

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

Sponsor

Ohio State University

Collaborators

Genzyme, a Sanofi Company

Investigators

  • Principal Investigator: Deborah M Grzybowski, PhD, Ohio State University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

July 1, 2010

Primary Completion (Actual)

July 1, 2014

Study Completion (Actual)

December 1, 2014

Study Registration Dates

First Submitted

July 16, 2010

First Submitted That Met QC Criteria

July 19, 2010

First Posted (Estimate)

July 20, 2010

Study Record Updates

Last Update Posted (Estimate)

January 13, 2017

Last Update Submitted That Met QC Criteria

January 11, 2017

Last Verified

January 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2009H0137

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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