Thrombocytopathy in Gaucher Disease Patients

Study Description

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

In Gaucher disease type I bleeding is a common presenting symptom, that may manifest itself as frequent nose bleeds, easy bruising but can also cause substantial bleeding after surgical or dental procedures and may occur in association with pregnancy or delivery . The bleeding tendency is usually considered to be secondary to thrombocytopenia However 50,000 platelets are enough in healthy people to give a normal bleeding time but are associated with significant bleeding tendencies in Gaucher patients. Bleeding tendency might be attributed by genetic inherited or Gaucher related coagulation factors abnormalities which in some cases stabilize with ERT. However, In other cases the etiology is an abnormality of platelet function. This thrombocytopathy has not been delineated and apart from a few aggregation studies, no systematic analysis has been published that convincingly shows the cause of the disturbed function. While, experience shows that enzyme replacement (ERT, i.e: imiglucerase, Cerezyme®) reduces this bleeding tendency, in part due to the improvement in the thrombocyte count and elevation in coagulation factors, it is less clear what effect ERT has on the thrombocytopathy. This has clinical significance when patients need to be prepared for surgery or delivery or in the event of a major bleed. There is no consensus as to how patients should be prepared or treated. Different centres use different approaches. When the procedure is elective ERT is appropriate but in other situations DDAVP, fresh frozen plasma and platelet infusion are possible treatments. Even activated factor VII has been used when bleeding was not controlled. As in any other coagulation abnormality, treatment should be tailored to the specific cause of the bleeding diathesis. The aim of this study is to define the etiology of platelet dysfunction in Gaucher patients.

Hypothesis: The investigators expect to see a difference between platelets activation profile among imiglucerase treated and untreated patients with at least a partial restoration of platelets function due to treatment commencement.

Condition or disease
Gaucher Disease; Thrombocytopathy

Detailed Description:

Objectives:

Delineating the cause of the thrombocytopathy in Gaucher disease patients:

1. Identifying thrombocytopathy among a cohort of 70 Gaucher patients managed (treated and untreated) in our clinic using a panel of platelets function tests.
2. Understanding the etiology for platelets dysfunction in Gaucher disease.
3. Evaluating the impact of Imiglucerase treatment duration and Gaucher disease severity on platelet function

Study Design

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Study Type :	Observational
Estimated Enrollment :	70 participants
Observational Model:	Case Control
Time Perspective:	Prospective
Official Title:	A 1.5 Years Prospective Study Designed to Delineate the Cause of the Thrombocytopathy in Gaucher Disease Patients
Study Start Date :	October 2010
Estimated Primary Completion Date :	November 2018
Estimated Study Completion Date :	November 2018

Groups and Cohorts

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Outcome Measures

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Measure thrombocytopathy in a cohort of 70 Gaucher patients using a set of platelet function tests. [ Time Frame: 3 years ]
   • 70 Gaucher patients managed (treated and untreated controls) will be subjected to a panel of platelets function tests (aggregation test, closure time and FACS analysis).

Secondary Outcome Measures :

1. Evaluating the impact of Imiglucerase treatment on platelet function [ Time Frame: 3 years ]
   Platelet function during the 3 years of study will be analyzed versus Imiglucerase treatment status and duration taking into consideration genotype, age at diagnosis, spleen status and Gaucher disease severity at treatment initiation

Biospecimen Retention:   Samples Without DNA

Blood Samples

Eligibility Criteria

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

Gaucher disease patients treated and untreated wih Imiglucerase

Criteria

Inclusion Criteria:

• Gaucher disease patients
• Patients who do not receive any medicine that affects platlats

Exclusion Criteria:

• Treatment with enzyme replacement therapy other than Imiglucerase

Contacts and Locations

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Contacts

Contact: Monica Weisz Hubshman, MD	972-3-9377522	MonicaWe@clalit.org.il
Contact: Ian J Cohen, Prof.		icohen@tau.ac.il

Locations

Israel
Rambam Medical Center	Not yet recruiting
Haifa, Israel
Contact: Hagit Baris, Prof 972-4-7771286 HB_Feldman@rambam.health.gov.il
Contact: Ian J Cohen, Prof icohen@tau.ac.il
Principal Investigator: Hagit Baris
Rabin Medical Center	Recruiting
Petach Tikva, Israel, 49100
Contact: Monica Weisz Hubshman, MD 972-3-9377522 MonicaWe@clalit.org.il
Contact: Ian J Cohen, Prof. icohen@tau.ac.il
Principal Investigator: Monica Weisz Hubshman, MD
Sub-Investigator: Ian Cohen, Prof.

Sponsors and Collaborators

Rabin Medical Center

Genzyme, a Sanofi Company

Investigators

Study Chair:	Ian J Cohen, Prof.	Rabin Medical Center
Study Chair:	Hagit Baris, MD	Rambam Health Care Campus

More Information

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Baris HN, Weisz Hubshman M, Bar-Sever Z, Kornreich L, Shkalim Zemer V, Cohen IJ. Re-evaluation of bone pain in patients with type 1 Gaucher disease suggests that bone crises occur in small bones as well as long bones. Blood Cells Mol Dis. 2016 Sep;60:65-72. doi: 10.1016/j.bcmd.2015.05.003. Epub 2015 May 9.

Responsible Party:	Rabin Medical Center
ClinicalTrials.gov Identifier:	NCT01344096 History of Changes
Other Study ID Numbers:	RMC6088; GZGD02507 ( Other Grant/Funding Number: Genzyme )
First Posted:	April 28, 2011
Last Update Posted:	October 28, 2016
Last Verified:	October 2016

Keywords provided by Rabin Medical Center:

Gaucher disease; Thrombocytopathy; Imiglucerase

Additional relevant MeSH terms:

Gaucher Disease; Blood Platelet Disorders; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases	Metabolism, Inborn Errors; Genetic Diseases, Inborn; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Lipid Metabolism Disorders; Hematologic Diseases