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Fabry DiseaseNCT02649660

Lipidomics and Functional Analyses of Platelets in Fabry Disease

An observational study of Fabry Disease, run by Spital Linth at 2 sites in Switzerland.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Fabry Disease
How many people
32 participants
Where
2 sitesSwitzerland
Study dates
Oct 2015to 31 Dec 2017
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Study population: Patients with Fabry Disease and healthy volunteers

Who may be able to join

  • 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

Who cannot join

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

Trial locations and contacts

2 sites in 1 country.

Pierre-Alexandre Krayenbühl, MD contact

+41 55 285 40 62

Pierre-Alexandre.Krayenbuehl@spital-linth.ch

Switzerland2 sites, 2 recruiting

  • Spital Linth

    Uznach, Canton of St. Gallen, 8730

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

    Pierre-Alexandre Krayenbuehl, MD

    Recruiting

  • University Hospital, Zürich

    Zurich, Canton of Zurich, 8091

    Albina Nowak, MD, +41 44 255 10 54, albina.nowak@usz.ch

    Albina Nowak, MD

    Recruiting

Other trials in Switzerland

About this study

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.

Read the 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
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
Medical subject headings
Fabry Disease, Lysosomal Storage Diseases

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline

  2. 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.

    Measured: Baseline

Secondary outcomes (7)

  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

    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.

    Measured: Baseline

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

    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.

    Measured: Baseline

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

    Plasma concentrations of soluble P-selectin (soluble CD62P) are determined by ELISA (enzyme-linked immunosorbent assay)

    Measured: Baseline

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

    Plasma concentrations of sCD40L (soluble CD40 ligand) are determined by ELISA (enzyme-linked immunosorbent assay)

    Measured: Baseline

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

    Flow cytometric assessment of platelet-platelet and platelet-leukocyte aggregates

    Measured: Baseline

  6. Differences of alpha-galactosidase A enzyme activity in plasma and isolated platelets between Fabry disease patients and healthy subjects

    Analysis of the alpha-galactosidase A enzyme activity using a fluorometric enzyme assay with 4-methylumbelliferyl-α-D-galactopyranoside as substrate.

    Measured: Baseline

  7. Differences in phospholipid profiles in platelets and plasma between Fabry disease patients and healthy subjects

    Determination of phospholipid concentrations in isolated platelets and plasma by targeted LC-MS-based lipidomics analysis of phosphatidylcholines, phosphatidylserines, phosphatidylinositols, and phosphatidylethanolamines.

    Measured: Baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jan 2016 (estimated)
  2. Study startOct 2015
  3. Primary completion31 Dec 2017 (estimated)
  4. Study completion31 Dec 2017 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Cross-sectional
Enrolment
32 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02649660
Sponsor's protocol ID
FabryPlatelets
Status last verified
May 2017
First submitted
6 Dec 2015
Last updated
8 May 2017
Results posted
No
Data monitoring committee
No

Publications

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

    PubMed 21776363

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

    PubMed 4701549

  • 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.

    PubMed 3620

  • 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.

    PubMed 19150871

  • 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.

    PubMed 3006478

  • 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.

    PubMed 10665494

  • 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.

    PubMed 19515805

Questions about this trial

What is this clinical trial studying?

An observational study of Fabry Disease, run by Spital Linth at 2 sites in Switzerland.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 8 May 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Pierre-Alexandre Krayenbühl, MD (+41 55 285 40 62, Pierre-Alexandre.Krayenbuehl@spital-linth.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Differences in sphingolipid profiles of platelets and plasma between Fabry disease patients and healthy subjects (time frame: Baseline). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02649660, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2017.

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