Ophthalmic Findings During 10-year Enzyme Substitution of Danish Fabry Patients.

NCT01997489 | Completed Phase 4

• 2 other identifiers: Fabry-Eyes-13RH-F-2013
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 2

Brief Summary

Fabry disease is a recessively inherited disorder due to systemic storage of abnormal metabolites (ceramide trihexocide, in particular) caused by lack of the lysosomal enzyme α-galactosidase. Though X-linked, in patient series there are often equal numbers of males (hemizygotes ) and females (heterozygotes, probably caused by a mutation in one allele and an inactivation on the other allele in the X chromosomes), and many clinical features are shared. Abnormal storage in endothelial and smooth muscle cells explains morbidity, including a shortened life expectancy. This is due to age dependent ischaemic manifestations that affect heart, kidney and brain. Angiofibroma is an early cutaneous manifestation, and painful acro-paresthesias express juvenile neuropathy. Cornea verticillata is an almost obligate ophthalmic finding. The brown-yellow Bowman membrane related corneal deposits and teleangiectatic conjunctival vessels are early ophthalmic slit-lamp markers of the disorder; further there can be subtle lens opacities. Fundus vessel tortuosity is observed in many patients, in particular of the retinal venules, but best corrected visual acuity (BCVA) is usually normal. After the introduction of enzyme substitution therapy in 2001, ophthalmic examinations were scheduled as regular part of the general evaluation of the Fabry patients at Rigshospitalet, Denmark. A 10-year ophthalmic state of arts was part of oral presentations at a Copenhagen conference in December 2011. In contrast to the common occurrence of systemic vascular sequels, only one patient in the series had suffered severe visual loss; this was unilateral and occurred years before institution of the enzyme therapy. In 2013, however, another young male presented a similar retinal event. Sporadic cases of visual loss are reported in the literature, but in larger Fabry series ocular vascular catastrophes appear the exception to the rule. Following the introduction of enzyme substitution, we found it of interest to present our nationwide Danish experience. We focused on retinal vessel morphology and the relation to systemic morbidity.

Conditions

Fabry Disease

Keywords

Eye; Fabry; vessels

Outcome Measures

Primary Outcomes (1)

• cornea vercillitata

  Eye examination of 39 Fabry patients before starting therapy with enzyme replacement and after 10 years

  change from baseline to 10 years

Study Arms (1)

Fabry patients during treatment

EXPERIMENTAL

39 patients with Fabry disease having had baseline examinations of the eyes were assessed also at follow-up 10 years after enzyme replacement therapy

Drug: Enzyme replacement

Interventions

Enzyme replacement DRUG

Observational study of current treatment and with no comparative groups

Also known as: Replagal, Fabrazyme

Fabry patients during treatment

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• All Danish patients with Fabry disease before starting therapy

You may not qualify if:

• Missing values for eye examination at baseline or follow-up

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead

Study Sites (2)

Ulla Feldt-Rasmussen

Copenhagen, Capital Region, DK-2100, Denmark

Location

National University Hospital, Department of Medical Endocrinology

Copenhagen, DK-2100, Denmark

Location

MeSH Terms

Conditions

Fabry Disease

Interventions

Enzyme Replacement Therapy; agalsidase alfa; agalsidase beta

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; Vascular Diseases; 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

Intervention Hierarchy (Ancestors)

Enzyme Therapy; Drug Therapy; Therapeutics

Study Officials

• Ulla Feldt-Rasmussen, MD, DMSc

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, chief physician

Study Record Dates

• First Submitted: November 18, 2013
• First Posted: November 28, 2013
• Study Start: September 1, 2001
• Primary Completion: September 1, 2013
• Study Completion: October 1, 2014
• Last Updated: October 28, 2014

Record last verified: 2014-10

Locations

DK (2)