Establishment of Biomarkers for Fabry Disease

NCT ID: NCT01165697

Last Updated: 2017-01-13

Study Results

Results pending

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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Recruitment Status

COMPLETED

Total Enrollment

4 participants

Study Classification

OBSERVATIONAL

Study Start Date

2010-07-31

Study Completion Date

2014-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Fabry Disease

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

PROSPECTIVE

Study Groups

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Fabry disease biomarker

Neuro-retinal fluorescein angiography (NRFA) exam will be administered once every 6 months for up to 3 years.

Fluorescein angiography

Intervention Type OTHER

Fluorescein angiography once every 6 months for 3 years

Interventions

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Fluorescein angiography

Fluorescein angiography once every 6 months for 3 years

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role collaborator

Ohio State University

OTHER

Sponsor Role lead

Responsible Party

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Deb Grzybowski

Research Assistant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Deborah M Grzybowski, PhD

Role: PRINCIPAL_INVESTIGATOR

Ohio State University

Locations

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Eye and Ear Institute

Columbus, Ohio, United States

Site Status

Countries

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United States

References

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Caggana M, Ashley GA, Desnick RJ, Eng CM. Fabry disease: molecular carrier detection and prenatal diagnosis by analysis of closely linked polymorphisms at Xq22.1. Am J Med Genet. 1997 Aug 22;71(3):329-35.

Reference Type BACKGROUND
PMID: 9268104 (View on PubMed)

Eng CM, Fletcher J, Wilcox WR, Waldek S, Scott CR, Sillence DO, Breunig F, Charrow J, Germain DP, Nicholls K, Banikazemi M. Fabry disease: baseline medical characteristics of a cohort of 1765 males and females in the Fabry Registry. J Inherit Metab Dis. 2007 Apr;30(2):184-92. doi: 10.1007/s10545-007-0521-2. Epub 2007 Mar 8.

Reference Type BACKGROUND
PMID: 17347915 (View on PubMed)

Wilcox WR, Oliveira JP, Hopkin RJ, Ortiz A, Banikazemi M, Feldt-Rasmussen U, Sims K, Waldek S, Pastores GM, Lee P, Eng CM, Marodi L, Stanford KE, Breunig F, Wanner C, Warnock DG, Lemay RM, Germain DP; Fabry Registry. Females with Fabry disease frequently have major organ involvement: lessons from the Fabry Registry. Mol Genet Metab. 2008 Feb;93(2):112-28. doi: 10.1016/j.ymgme.2007.09.013. Epub 2007 Nov 26.

Reference Type BACKGROUND
PMID: 18037317 (View on PubMed)

Glass RB, Astrin KH, Norton KI, Parsons R, Eng CM, Banikazemi M, Desnick RJ. Fabry disease: renal sonographic and magnetic resonance imaging findings in affected males and carrier females with the classic and cardiac variant phenotypes. J Comput Assist Tomogr. 2004 Mar-Apr;28(2):158-68. doi: 10.1097/00004728-200403000-00002.

Reference Type BACKGROUND
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Eng CM, Germain DP, Banikazemi M, Warnock DG, Wanner C, Hopkin RJ, Bultas J, Lee P, Sims K, Brodie SE, Pastores GM, Strotmann JM, Wilcox WR. Fabry disease: guidelines for the evaluation and management of multi-organ system involvement. Genet Med. 2006 Sep;8(9):539-48. doi: 10.1097/01.gim.0000237866.70357.c6.

Reference Type BACKGROUND
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Svarstad E, Bostad L, Kaarboe O, Houge G, Tondel C, Lyngdal PT, Iversen BM. Focal and segmental glomerular sclerosis (FSGS) in a man and a woman with Fabry's disease. Clin Nephrol. 2005 May;63(5):394-401. doi: 10.5414/cnp63394.

Reference Type BACKGROUND
PMID: 15909601 (View on PubMed)

Tondel C, Bostad L, Hirth A, Svarstad E. Renal biopsy findings in children and adolescents with Fabry disease and minimal albuminuria. Am J Kidney Dis. 2008 May;51(5):767-76. doi: 10.1053/j.ajkd.2007.12.032. Epub 2008 Mar 20.

Reference Type BACKGROUND
PMID: 18436087 (View on PubMed)

Tondel C, Bostad L, Laegreid LM, Houge G, Svarstad E. Prominence of glomerular and vascular changes in renal biopsies in children and adolescents with Fabry disease and microalbuminuria. Clin Ther. 2008;30 Suppl B:S42. doi: 10.1016/s0149-2918(08)80036-7. No abstract available.

Reference Type BACKGROUND
PMID: 18395135 (View on PubMed)

Tondel C, Laegreid LM, Hirth A, Houge G, Mansson JE, Sovik O. [Intravenous enzyme substitution therapy in children with Fabry's disease]. Tidsskr Nor Laegeforen. 2003 Dec 4;123(23):3388-90. Norwegian.

Reference Type BACKGROUND
PMID: 14713976 (View on PubMed)

Strujic BJ, Jeren T. Fabry disease--a diagnostic and therapeutic problem. Ren Fail. 2005;27(6):783-6. doi: 10.1080/08860220500244856.

Reference Type BACKGROUND
PMID: 16350834 (View on PubMed)

Gilbert-Barness E. Review: Metabolic cardiomyopathy and conduction system defects in children. Ann Clin Lab Sci. 2004 Winter;34(1):15-34.

Reference Type BACKGROUND
PMID: 15038665 (View on PubMed)

Kampmann C, Wiethoff CM, Perrot A, Beck M, Dietz R, Osterziel KJ. The heart in Anderson Fabry disease. Z Kardiol. 2002 Oct;91(10):786-95. doi: 10.1007/s00392-002-0848-5.

Reference Type BACKGROUND
PMID: 12395219 (View on PubMed)

Whybra C, Kampmann C, Willers I, Davies J, Winchester B, Kriegsmann J, Bruhl K, Gal A, Bunge S, Beck M. Anderson-Fabry disease: clinical manifestations of disease in female heterozygotes. J Inherit Metab Dis. 2001 Dec;24(7):715-24. doi: 10.1023/a:1012993305223.

Reference Type BACKGROUND
PMID: 11804208 (View on PubMed)

Mitsias P, Levine SR. Cerebrovascular complications of Fabry's disease. Ann Neurol. 1996 Jul;40(1):8-17. doi: 10.1002/ana.410400105.

Reference Type BACKGROUND
PMID: 8687196 (View on PubMed)

Mehta A, Ginsberg L; FOS Investigators. Natural history of the cerebrovascular complications of Fabry disease. Acta Paediatr Suppl. 2005 Mar;94(447):24-7; discussion 9-10. doi: 10.1111/j.1651-2227.2005.tb02106.x.

Reference Type BACKGROUND
PMID: 15895708 (View on PubMed)

Michels H, Mengel E. Lysosomal storage diseases as differential diagnoses to rheumatic disorders. Curr Opin Rheumatol. 2008 Jan;20(1):76-81. doi: 10.1097/BOR.0b013e3282f169fe.

Reference Type BACKGROUND
PMID: 18281861 (View on PubMed)

Knowles SR, Weber EA, Berbrayer CS. Allergic reaction to fluorescein dye: successful one-day desensitization. Can J Ophthalmol. 2007 Apr;42(2):329-30.

Reference Type BACKGROUND
PMID: 17392867 (View on PubMed)

Cook SC, Ferketich AK, Raman SV. Myocardial ischemia in asymptomatic adults with repaired aortic coarctation. Int J Cardiol. 2009 Mar 20;133(1):95-101. doi: 10.1016/j.ijcard.2007.12.015. Epub 2008 Feb 11.

Reference Type BACKGROUND
PMID: 18262666 (View on PubMed)

Other Identifiers

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2009H0137

Identifier Type: -

Identifier Source: org_study_id

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