Establishment of Biomarkers for Fabry Disease

NCT01165697 | Completed

• 1 other identifier: 2009H0137
• Study Type: observational
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Fabry Disease

Keywords

Fabry Disease; vascular disease; storage endotheliopathy

Outcome Measures

Primary Outcomes (1)

• Presence of specific findings commonly associated with Fabry's disease using neuroretinal examination

  every 6 months, for up to 3 years

Secondary Outcomes (1)

• Capillary perfusion abnormalities in optic nerve and retina

  every 6 months, for up to 3 years

Study Arms (1)

Fabry disease biomarker

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

Other: Fluorescein angiography

Interventions

Fluorescein angiography OTHER

Fluorescein angiography once every 6 months for 3 years

Fabry disease biomarker

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ohio State University: lead
• Genzyme, a Sanofi Company: collaborator

Study Sites (1)

Eye and Ear Institute

Columbus, Ohio, 43212, United States

Location

Related Publications (18)

• 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.

  PMID: 9268104 BACKGROUND

• 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.

  PMID: 17347915 BACKGROUND

• 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.

  PMID: 18037317 BACKGROUND

• 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.

  PMID: 15091117 BACKGROUND

• 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.

  PMID: 16980809 BACKGROUND

• 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.

  PMID: 15909601 BACKGROUND

• 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.

  PMID: 18436087 BACKGROUND

• 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.

  PMID: 18395135 BACKGROUND

• 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.

  PMID: 14713976 BACKGROUND

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

  PMID: 16350834 BACKGROUND

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

  PMID: 15038665 BACKGROUND

• 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.

  PMID: 12395219 BACKGROUND

• 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.

  PMID: 11804208 BACKGROUND

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

  PMID: 8687196 BACKGROUND

• 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.

  PMID: 15895708 BACKGROUND

• 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.

  PMID: 18281861 BACKGROUND

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

  PMID: 17392867 BACKGROUND

• 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.

  PMID: 18262666 BACKGROUND

MeSH Terms

Conditions

Fabry Disease; Vascular Diseases

Condition Hierarchy (Ancestors)

Sphingolipidoses; 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; Cardiovascular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Study Officials

• Deborah M Grzybowski, PhD

  Ohio State University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Assistant Professor

Study Record Dates

• First Submitted: July 16, 2010
• First Posted: July 20, 2010
• Study Start: July 1, 2010
• Primary Completion: July 1, 2014
• Study Completion: December 1, 2014
• Last Updated: January 13, 2017

Record last verified: 2017-01

Locations

US (1)