Biomarker for Gaucher Disease (BioGaucher)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by University of Rostock
Sponsor:
Information provided by (Responsible Party):
Prof. Dr. Arndt Rolfs, University of Rostock
ClinicalTrials.gov Identifier:
NCT01331642
First received: April 6, 2011
Last updated: June 3, 2014
Last verified: June 2014
  Purpose

Gaucher disease is an autosomal recessive hereditary lysosomal storage disorder. Occurrence of the disease is due to a hereditary deficiency of the Glucocerebrosidase, a lysosomal enzyme which divides Glucocerebroside in to Glucose and Ceramides.


Condition
Lysosomal Storage Diseases
Gaucher Disease
Sphingolipidoses

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Biomarker for Gaucher Disease AN INTERNATIONAL, MULTICENTER, EPIDEMIOLOGICAL PROTOCOL

Resource links provided by NLM:


Further study details as provided by University of Rostock:

Biospecimen Retention:   Samples With DNA

For the development of the new biomarkers using the technique of Mass-spectometry 5ml EDTA blood and a dry blood spot filter card are taken. To proof the correct Gaucher diagnosis in those patients where up to the enrollment in the study no genetic testing has been done, sequencing of Gaucher will be done. The analyses are done in the Albrecht-Kossel-Institute for Neuroregeneration (AKos), POB 100 888, Gehlsheimer Str. 20, 18055 Rostock (Germany)


Estimated Enrollment: 200
Study Start Date: April 2011
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
Observation
Patients from the first day of life with Gaucher Disease based on biochemical and/or genetic criteria or high-grade suspicion for Gaucher disease.

Detailed Description:

The unmetabolised Glucocerebrosides are stored throughout the whole reticulo-endothelial system. Accumulation of Glycolipid-enriched Macrophages establishes a pathoanatomical phenomenon, the so-called Gaucher cells, which can be verified by light microscopy. Activation markers of the Macrophages, like the enzyme Chitotriosidase or CCL18, are parameters which follow the course of Gaucher dis-ease. Gaucher disease is the most frequently inherited Sphingolipidosis in the general population, and in Ahskenazi Jews, in who the prevalence is much higher (1:450). The gene which codes the Glucocerebrosidase is on the long arm of chromosome 1 and covers 11 exons. So far, more than 200 different mutations in Gaucher patients have been described, mostly missense mutations. In addition frame-shift- and splice-site-mutations have been detected, as well as insertions and deletions. More frequent mutations are N370S, L444P, IVS2+1G>A, c.84insG, R463C and R496H [Sidransky E. 2004]. The clinical appearance is heterogeneous. The classical phenotype is characterized by visceral organ (Hepatosplenomegaly) and skeleton system (Bone marrow infiltrates up to bone infarcts and pathological fractures) affection. Moreover, consecutive blood cell count changes, Anemia and Thrombocytopenia are reported.A serious distinction lies in the appearance of neurological manifestations (myoclonus epilepsy, hydrocephalus, ocular movement disturbances). There is discussion on whether the classification into the typical three disease types (type1: non-neuronopathic progress form, type2: acute neuronopathic progress form, type3: chronic neuronopathic progress form) is still up-to-date, since it does not sufficiently reflect the reality of the clinical presentation. A clear genotype-phenotype relationship does not exist. The same DNA mutations are detected in patients with pronounced differences in disease progression. The exception is the mutation N370S, which has so far been detected in connection with only visceral progress forms (type1) [Koprivica et al. 2000]. At least the outcome of the non-neuronopathic disorder cases could be improved by the introduction and general availability of enzyme therapy. Under this kind of therapy there is a reduction of liver and spleen size as well as a normalization of the haemogram parameters.

New methods, like mass-spectrometry give a good chance to characterize in the blood (plasma) of affected patents specific metabolic alterations that allow to diagnose in the future the disease earlier, with a higher sensitivity and specificity. The development of new bio-chemical markers from the plasma of the affected patients is the goal of the study.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Patients with Gaucher Disease based on biochemical and/or genetic criteria or high-grade suspicion for Gaucher disease.

Criteria

Inclusion Criteria:

  • Informed consent will be obtained from the patient or the parents before any study related procedures.
  • Patients from the first day of life
  • The patient has a diagnosis of Gaucher Disease based on biochemical and/or genetic criteria or high-grade suspicion for Gaucher disease

High-grade suspicion present, if one or more inclusion criteria are valid:

  • Positive family anamnesis for Gaucher disease
  • Splenomegaly without identifiable cause
  • Hepatomegaly without identifiable cause
  • Anemia or thrombocytopenia without identifiable cause CNS involvement without identifiable cause

Exclusion Criteria:

  • No Informed consent from the patient or the parents before any study related procedures
  • No diagnosis of Gaucher disease or no valid criteria for profound suspicion of Gaucher disease
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01331642

Contacts
Contact: Arndt Rolfs, MD +49 381 494 ext 9540 arndt.rolfs@med.uni-rostock.de
Contact: Susanne Zielke +49 381 494 ext 4739 susanne.zielke@med.uni-rostock.de

Locations
Algeria
Pediatric practice Recruiting
Oran, Algeria, 31000
Contact: Abdelmadjid Benmansour, MD       benmansour_b@yahoo.com   
Principal Investigator: Abdelmadjid Benmansour, MD         
Brazil
Health Technology Assessment in Clinical Genetics Research Group Not yet recruiting
Porto Alegre -RS, Brazil, 90035-003
Contact: Ida Vanessa Schwartz, Prof       idadschwartz@gmail.com   
Principal Investigator: Ida Vanessa Schwartz, Prof.         
Clinics Hospital of Ribeirao Preto- University of Sao Paulo Recruiting
Sao Paulo, Brazil, 14048-900
Contact: Charles Marques Lourenco, MD       charlesgenetica@gmail.com   
Principal Investigator: Charles Marques Lourenco, MD         
Germany
University of Rostock, Albrecht-Kossel Institute Recruiting
Rostock, Germany, 18147
Contact: Susanne Zielke    49-381-494 ext 4739    susanne.zielke@med.uni-rostock.de   
Principal Investigator: Arndt Rolfs, MD         
Greece
Aristotle University of Thessaloniki-Ippokration General Hospital Recruiting
Thessaloniki, Greece, 54642
Contact: Dimitrios Zafeiriou, MD       jeff@med.auth.gr   
Principal Investigator: Dimitrios Zafeiriou, MD         
India
NIRMAN, University of Mumbai Recruiting
Mumbai, India, 400705
Contact: Anil Jalan, MD       jalananil@yahoo.com   
Principal Investigator: Anil Jalan, MD         
Serbia
Mother and Child Health Institute of Serbia Recruiting
Novi-Beograd, Serbia, 11070
Contact: Adrijan Sarajlija, MD       adrijans2004@yahoo.com   
Principal Investigator: Adrijan Sarajlija, MD         
Sponsors and Collaborators
University of Rostock
Investigators
Principal Investigator: Arndt Rolfs, MD University of Rostock, Albrecht-Kossel-Institute for Neuroregeneration
  More Information

Additional Information:
No publications provided

Responsible Party: Prof. Dr. Arndt Rolfs, University of Rostock
ClinicalTrials.gov Identifier: NCT01331642     History of Changes
Other Study ID Numbers: BG05/2011
Study First Received: April 6, 2011
Last Updated: June 3, 2014
Health Authority: Germany: Ethics Commission

Keywords provided by University of Rostock:
Lymphatic Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lipidoses
Lipid Metabolism, Inborn Errors
Metabolic Diseases
Lipid Metabolism Disorders

Additional relevant MeSH terms:
Gaucher Disease
Sphingolipidoses
Lipid Metabolism Disorders
Lysosomal Storage Diseases
Metabolic Diseases
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

ClinicalTrials.gov processed this record on July 20, 2014