Lipidomics and Functional Analyses of Platelets in Fabry Disease

NCT02649660 | Unknown

• 1 other identifier: FabryPlatelets
• Study Type: observational
• Target: 32
• Locations: 1 country
• Sites: 2

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.

Conditions

Fabry Disease

Keywords

Fabry Disease; Platelets; Lipidomics; Sphingolipids; α-Galactosidase A; Globotriaosylceramide; Gb3; GL-3; CD77; Alpha-galactosidase; Platelet activation; Lysosomal storage disease; LysoGb3; Spingosine-1-Phosphate; Platelet function; CD62P; P-selectin

Outcome Measures

Primary Outcomes (2)

• Differences in sphingolipid profiles of platelets and plasma between Fabry disease patients and healthy subjects

  Determination of sphingolipid concentrations in isolated platelets and plasma by targeted LC-MS (liquid chromatography mass spectrometry)-based lipidomics analysis of globotriaosylceramides (Gb3), globotriaosylspingosines (Lyso-Gb3), globotetraosylceramides (Gb4), lactosylceramides (LacCer), glucosylceramides, ceramides, sphingomyelins, sphingosines and sphingosine-1-phosphates.

  Baseline

• Differences in platelet function assessed by aggregometry

  Determination of platelet aggregation after agonist stimulation with TRAP (thrombin receptor activator peptide), ADP (adenosine disphosphate) and arachidonic acid by light transmission aggregometry.

  Baseline

Secondary Outcomes (7)

• Differences in expression of the platelet activation marker P-selectin (CD62P) between Fabry disease patients and healthy subjects at baseline and after agonist stimulation

  Baseline

• Differences in expression of the platelet activation marker CD63 between Fabry disease patients and healthy subjects at baseline and after agonist stimulation

  Baseline

• Differences in plasma levels of the platelet activation marker soluble P-selectin between Fabry disease patients and healthy subjects

  Baseline

• Differences in plasma levels of the platelet activation marker sCD40L between Fabry disease patients and healthy subjects

  Baseline

• Differences in presence of platelet aggregates between Fabry disease patients and healthy subjects

  Baseline

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with Fabry Disease and healthy volunteers

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Spital Linth: lead
• University of Zurich: collaborator
• National University of Singapore: collaborator

Study Sites (2)

Spital Linth

Uznach, Canton of St. Gallen, 8730, Switzerland

RECRUITING

University Hospital, Zürich

Zurich, Canton of Zurich, 8091, Switzerland

RECRUITING

Related Publications (7)

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

  PMID: 21776363 BACKGROUND

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

  PMID: 4701549 BACKGROUND

• 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.

  PMID: 3620 BACKGROUND

• 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.

  PMID: 19150871 RESULT

• 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.

  PMID: 3006478 RESULT

• 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.

  PMID: 10665494 RESULT

• 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.

  PMID: 19515805 RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood plasma, serum and platelet isolates

MeSH Terms

Conditions

Fabry Disease; Lysosomal Storage 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; 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; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Study Officials

• Pierre-Alexandre Krayenbühl, MD

  Spital Linth

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pierre-Alexandre Krayenbühl, MD

CONTACT

+41 55 285 40 62; Pierre-Alexandre.Krayenbuehl@spital-linth.ch

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2015
• First Posted: January 7, 2016
• Study Start: October 1, 2015
• Primary Completion: December 31, 2017
• Study Completion: December 31, 2017
• Last Updated: May 8, 2017

Record last verified: 2017-05

Locations

CH (2)