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Trial record 15 of 153 for:    "Fabry disease"

Lipidomics and Functional Analyses of Platelets in Fabry Disease

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ClinicalTrials.gov Identifier: NCT02649660
Recruitment Status : Unknown
Verified May 2017 by Spital Linth.
Recruitment status was:  Recruiting
First Posted : January 7, 2016
Last Update Posted : May 8, 2017
Sponsor:
Collaborators:
University of Zurich
National University, Singapore
Information provided by (Responsible Party):
Spital Linth

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.

Condition or disease
Fabry Disease

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.


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Study Type : Observational
Estimated Enrollment : 32 participants
Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Lipidomics and Functional Analyses of Platelets in Fabry Disease
Study Start Date : October 2015
Estimated Primary Completion Date : December 31, 2017
Estimated Study Completion Date : December 31, 2017

Resource links provided by the National Library of Medicine





Primary Outcome Measures :
  1. Differences in sphingolipid profiles of platelets and plasma between Fabry disease patients and healthy subjects [ Time Frame: Baseline ]
    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.

  2. Differences in platelet function assessed by aggregometry [ Time Frame: Baseline ]
    Determination of platelet aggregation after agonist stimulation with TRAP (thrombin receptor activator peptide), ADP (adenosine disphosphate) and arachidonic acid by light transmission aggregometry.


Secondary Outcome Measures :
  1. Differences in expression of the platelet activation marker P-selectin (CD62P) between Fabry disease patients and healthy subjects at baseline and after agonist stimulation [ Time Frame: Baseline ]
    Flow cytometric analysis of platelet surface expression of CD62P in whole blood determined at baseline and after platelet activation with the agonists TRAP (thrombin receptor activator peptide), ADP, and arachidonic acid.

  2. Differences in expression of the platelet activation marker CD63 between Fabry disease patients and healthy subjects at baseline and after agonist stimulation [ Time Frame: Baseline ]
    Flow cytometric analysis of platelet surface expression of CD63 in whole blood determined at baseline and after platelet activation with the agonists TRAP (thrombin receptor activator peptide), ADP, and arachidonic acid.

  3. Differences in plasma levels of the platelet activation marker soluble P-selectin between Fabry disease patients and healthy subjects [ Time Frame: Baseline ]
    Plasma concentrations of soluble P-selectin (soluble CD62P) are determined by ELISA (enzyme-linked immunosorbent assay)

  4. Differences in plasma levels of the platelet activation marker sCD40L between Fabry disease patients and healthy subjects [ Time Frame: Baseline ]
    Plasma concentrations of sCD40L (soluble CD40 ligand) are determined by ELISA (enzyme-linked immunosorbent assay)

  5. Differences in presence of platelet aggregates between Fabry disease patients and healthy subjects [ Time Frame: Baseline ]
    Flow cytometric assessment of platelet-platelet and platelet-leukocyte aggregates

  6. Differences of alpha-galactosidase A enzyme activity in plasma and isolated platelets between Fabry disease patients and healthy subjects [ Time Frame: Baseline ]
    Analysis of the alpha-galactosidase A enzyme activity using a fluorometric enzyme assay with 4-methylumbelliferyl-α-D-galactopyranoside as substrate.

  7. Differences in phospholipid profiles in platelets and plasma between Fabry disease patients and healthy subjects [ Time Frame: Baseline ]
    Determination of phospholipid concentrations in isolated platelets and plasma by targeted LC-MS-based lipidomics analysis of phosphatidylcholines, phosphatidylserines, phosphatidylinositols, and phosphatidylethanolamines.


Biospecimen Retention:   Samples Without DNA
Blood plasma, serum and platelet isolates


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Patients with Fabry Disease and healthy volunteers
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

Exclusion Criteria:

  • Failure to meet inclusion criteria
  • Pregnancy (as declared by the study participant, no pregnancy test will be performed)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02649660


Contacts
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Contact: Pierre-Alexandre Krayenbühl, MD +41 55 285 40 62 Pierre-Alexandre.Krayenbuehl@spital-linth.ch

Locations
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Switzerland
Spital Linth Recruiting
Uznach, SG, Switzerland, 8730
Contact: Pierre-Alexandre Krayenbuehl, MD    +41 55 285 40 62    Pierre-Alexandre.Krayenbuehl@spital-linth.ch   
Principal Investigator: Pierre-Alexandre Krayenbuehl, MD         
University Hospital, Zürich Recruiting
Zürich, ZH, Switzerland, 8091
Contact: Albina Nowak, MD    +41 44 255 10 54    albina.nowak@usz.ch   
Principal Investigator: Albina Nowak, MD         
Sub-Investigator: Jan-Dirk Studt, MD         
Sponsors and Collaborators
Spital Linth
University of Zurich
National University, Singapore
Investigators
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Principal Investigator: Pierre-Alexandre Krayenbühl, MD Spital Linth

Publications of Results:
Other Publications:
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Responsible Party: Spital Linth
ClinicalTrials.gov Identifier: NCT02649660     History of Changes
Other Study ID Numbers: FabryPlatelets
First Posted: January 7, 2016    Key Record Dates
Last Update Posted: May 8, 2017
Last Verified: May 2017

Keywords provided by Spital Linth:
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

Additional relevant MeSH terms:
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Fabry Disease
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
Metabolism, Inborn Errors
Lipidoses
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders