Lipidomics and Functional Analyses of Platelets in Fabry Disease

NCT ID: NCT02649660

Last Updated: 2017-05-08

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 32 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-10-31
• Study Completion Date: 2017-12-31

Brief Summary

This study aims to evaluate whether platelets are biochemically and functionally altered in Fabry disease (FD) and therefore possibly implicated in FD manifestations such as cerebrovascular events. To test this hypothesis the investigators aim to compare platelet and plasma lipid profiles, as well as platelet function and coagulation parameters of FD patients and healthy controls.

Detailed Description

Fabry disease (FD) is a severe X-linked inborn error of the lysosomal glycosphingolipid metabolism. FD patients have significantly increased risks for cardiac and cerebrovascular events, which can also occur early and in absence of the typical FD symptoms. However, the pathophysiological mechanisms leading to vascular occlusion and ischemia in FD are largely unclear. Prevention of recurrent cerebrovascular events is usually based on empirical anti-platelet therapy.

Prothrombotic states and partially activated platelets have been reported for FD patients. Platelets contain glycosphingolipids, including globotriaosylceramide (Gb3), and have lysosomal α-galactosidase activity. To investigate whether the lack of or the reduced α-galactosidase enzyme activity present in Fabry disease affects platelet lipid metabolism the investigators plan to perform LC-MS-based lipidomics analyses of platelets and plasma in FD patients and healthy controls. To assess whether platelets are functionally altered in FD, the investigators aim to determine the activation status, activability, aggregability and other parameters along with plasma markers of coagulation using flow cytometry, aggregometry and immunoassays.

Conditions

Fabry Disease

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: CROSS_SECTIONAL

Eligibility Criteria

Inclusion Criteria

• Healthy Volunteers: without any known cardiovascular, cerebrovascular and renal diseases and without any known conditions affecting platelet function, blood coagulation and lipid metabolism.
• Patients: Genetically confirmed Fabry Disease
• Adult persons (18-65 years old), both female and male
• Informed written consent

• Pregnancy (as declared by the study participant, no pregnancy test will be performed)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Zurich

OTHER

Sponsor Role: collaborator

National University of Singapore

OTHER

Sponsor Role: collaborator

Spital Linth

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pierre-Alexandre Krayenbühl, MD

Role: PRINCIPAL_INVESTIGATOR

Spital Linth

Locations

Spital Linth

Uznach, Canton of St. Gallen, Switzerland

Site Status: RECRUITING

University Hospital, Zürich

Zurich, Canton of Zurich, Switzerland

Site Status: RECRUITING

Countries

Switzerland

Central Contacts

Pierre-Alexandre Krayenbühl, MD

Role: CONTACT

Pierre-Alexandre.Krayenbuehl@spital-linth.ch

+41 55 285 40 62

Facility Contacts

Pierre-Alexandre Krayenbuehl, MD

Role: primary

Pierre-Alexandre.Krayenbuehl@spital-linth.ch

+41 55 285 40 62

Albina Nowak, MD

Role: primary

albina.nowak@usz.ch

+41 44 255 10 54

References

Feldt-Rasmussen U. Fabry disease and early stroke. Stroke Res Treat. 2011;2011:615218. doi: 10.4061/2011/615218. Epub 2011 Jun 23.

Reference Type: BACKGROUND

PMID: 21776363 (View on PubMed)

Tao RV, Sweeley CC, Jamieson GA. Sphingolipid composition of human platelets. J Lipid Res. 1973 Jan;14(1):16-25.

Reference Type: BACKGROUND

PMID: 4701549 (View on PubMed)

Beutler E, Kuhl W, Matsumoto F, Pangalis G. Acid hydrolases in leukocytes and platelets of normal subjects and in patients with Gaucher's and Fabry's disease. J Exp Med. 1976 Apr 1;143(4):975-80. doi: 10.1084/jem.143.4.975.

Reference Type: BACKGROUND

PMID: 3620 (View on PubMed)

Sims K, Politei J, Banikazemi M, Lee P. Stroke in Fabry disease frequently occurs before diagnosis and in the absence of other clinical events: natural history data from the Fabry Registry. Stroke. 2009 Mar;40(3):788-94. doi: 10.1161/STROKEAHA.108.526293. Epub 2009 Jan 15.

Reference Type: RESULT

PMID: 19150871 (View on PubMed)

Igarashi T, Sakuraba H, Suzuki Y. Activation of platelet function in Fabry's disease. Am J Hematol. 1986 May;22(1):63-7. doi: 10.1002/ajh.2830220110.

Reference Type: RESULT

PMID: 3006478 (View on PubMed)

DeGraba T, Azhar S, Dignat-George F, Brown E, Boutiere B, Altarescu G, McCarron R, Schiffmann R. Profile of endothelial and leukocyte activation in Fabry patients. Ann Neurol. 2000 Feb;47(2):229-33.

Reference Type: RESULT

PMID: 10665494 (View on PubMed)

Vedder AC, Biro E, Aerts JM, Nieuwland R, Sturk G, Hollak CE. Plasma markers of coagulation and endothelial activation in Fabry disease: impact of renal impairment. Nephrol Dial Transplant. 2009 Oct;24(10):3074-81. doi: 10.1093/ndt/gfp263. Epub 2009 Jun 10.

Reference Type: RESULT

PMID: 19515805 (View on PubMed)

Other Identifiers

FabryPlatelets

Identifier Type: -

Identifier Source: org_study_id