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Prevalence of Fabry Disease in a Defined Population at Risk - Patients Formerly Diagnosed With Multiple Sclerosis

This study is currently recruiting participants.
Verified March 2013 by University of Rostock
Sponsor:
Information provided by (Responsible Party):
Prof. Dr. Arndt Rolfs, University of Rostock
ClinicalTrials.gov Identifier:
NCT01271699
First received: January 6, 2011
Last updated: March 15, 2013
Last verified: March 2013
History of Changes
  Purpose

The association of Multiple Sclerosis (MS) and Fabry disease is known from own clinical experiences as well as from case reports in the literature, where symptoms and suspicious results in the brain MRI led to the misdiagnosis of Fabry patients as MS. Remarkably, those patients almost never showed oligoclonal bands or an intrathecally derived IgG-production was wrongly assumed due to misinterpretation of CSF results. Where oligoclonal bands were present, concomitant diagnoses had to be discussed. Furthermore, those patients showed no involvement of the spinal cord, as evidenced by MRI. Beside the possible complications of a not-effective and not-necessary MS therapy, those patients are at risk of irreparable organ damage due to the delayed implementation of enzyme replacement therapy for Fabry disease.


Condition
Multiple Sclerosis

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Multiple Sclerosis and Fabry Disease: Prevalence of Fabry Disease in a Defined Population at Risk - Patients Formerly Diagnosed With Multiple Sclerosis - an Epidemiological Study

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Rostock:

Biospecimen Retention:   Samples With DNA

Fabry diagnostic will be done centrally: blood samples will be stored for analysis of a-galactosidase in blood, Gb3 as well as lyso-Gb3. In all cases direct analysis of the gene will be done, especially in females where due to the Lyonisation effect a-galactosidase activity might be normal in blood although the patient might suffer from Fabry disease.


Estimated Enrollment: 250
Study Start Date: January 2011
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
Observation
Patients at age 18-50 with a confirmed or probably diagnosis of Multiple Sclerosis according to the McDonald diagnostic criteria for MS

Detailed Description:

Fabry disease is an X-linked lysosomal disorder that leads to excessive deposition of neutral glycosphingolipids in the vascular endothelium of several organs in the body. Progressive endothelial accumulation of glycosphingolipids accounts for the associated clinical abnormalities of skin, eye, kidney, heart, brain, and peripheral nervous system. Fabry disease manifesting predominantly in men. Female heterozygotes also present with features of Fabry disease. In Europe the prevalence of Fabry disease seems to be massively underrepresented.

Multiple Sclerosis (MS, Encephalomyelitis disseminata) ist the most common inflammatory disease of the central nervous system (CNS). The first clinical manifestation peaks in the 3rd-4th decade. 2.5 million Young adults are affected worldwide. In Germany the prevalence rate reaches approx. 100 patients per 100,000 inhabitants. Females are more frequently affected (2-3:1). The underlying causes of the disease are not sufficiently explored yet. The genetic backgrounds as well as environmental factors are involved. An autoimmune mediated process, driven by activated T-lymphocytes and macrophages, leads to inflammatory demyelination and axonal loss.

Magnetresonance imaging of the brain and spinal cord, evaluation of the cerebrospinal fluid to detect intrathecally derived immunoglobulin production (IgG) and a comprehensive diagnostic workup on other possible causes of the symptoms. The modern diagnostic criteria (McDonald criteria, 2001 + revisions 2005) demand the proof of the dissemination of the inflammatory process in space and time, either by clinical or radiological terms.

The evaluation of the cerebrospinal fluid aims at the confirmation of an intrathecally derived synthesis of IgG. In 98% of the patients oligoclonal bands can be detected during the course of the disease. This parameter is highly sensitive but only low specific. The diagnostic criteria allow making the diagnosis of "certain" or at least "probable" MS without the confirmation of oligoclonal bands.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Adult Patients at age 18-50 with a confirmed or probably diagnosis of Multiple Sclerosis according to the McDonald diagnostic criteria for Multiple Sclerosis

Criteria

Inclusion Criteria:

  • Patients at age 18-50 years old with a confirmed or probably diagnosis of Multiple Sclerosis according to the McDonald diagnostic criteria for MS
  • Patients with confirmed diagnosis of Multiple Sclerosis according to the McDonald diagnostic criteria but without confirmation of oligoclonal IgG in the CSF
  • Patients with present oligoclonal IgG in the CSF but without proof of dissemination of spinal inflammatory processes in the MRI
  • Signed informed consent

Exclusion Criteria:

  • Patients being younger than 18 years or older than 50 years
  • Patients without performed MRI of the brain and spinoaxis
  • Patients with a structural change in the brain that is not caused by a chronic inflammatory disease of the CNS
  • Missing signed informed consent
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01271699

Contacts
Contact: Arndt Rolfs, MD 49-381-494 ext 9540 arndt.rolfs@med.uni-rostock.de
Contact: Sabine Roesner 49-381-494 ext 4797 sabine.roesner@med.uni-rostock.de

Locations
Germany
Universitätsklinikum Aachen, Klink für Neurologie Recruiting
Aachen, Germany, 52074
Contact: Jörg Schulz, Prof. MD     0049 2418089600     jschulz@ukaachen.de    
Sub-Investigator: Simone Tauber, MD            
Kamillusklinik, Abtl. Neurologie Recruiting
Asbach, Germany, 53567
Contact: Dieter Pöhlau, MD     0049 2683 59 663     dieter.pöhlau@kamillus-klinik.de    
Sub-Investigator: Anka Liebezeit, MD            
Berlin Charite, Klinisches und experimentelles Forschungszentrum für Multiple Sklerose Recruiting
Berlin, Germany, 10117
Contact: Klemens Ruprecht, MD     0049 30450560374     klemens.ruprecht@charite.de    
Principal Investigator: Klemens Ruprecht, MD            
Jüdisches Krankenhaus Berlin, Abt. Neurologie Recruiting
Berlin, Germany, 13347
Contact: Haas Judith, Prof. MD     0049 30 4994 2348     haas@jkb-online.de    
Sub-Investigator: Marko Chatzopoulos, MD            
Sub-Investigator: Stephan Haack, MD            
HHU Düsseldorf, Klinik und Poliklinik für Neurologie Recruiting
Düsseldorf, Germany, 40225
Contact: Orhan Aktas, Prof. MD     0049 2118104169     Orhan.Aktas@uni-duesseldorf.de    
Sub-Investigator: Marius Ringelstein, MD            
Alfried Krupp Krankenhaus Rüttenscheid, Abt. Neurologie Recruiting
Essen, Germany, 45131
Contact: Markus Krämer, MD     0049 20143441424     markus.kraemer@krupp-krankenhaus.de    
Principal Investigator: Markus Krämer, MD            
Universitätsklinikum Gießen und Marburg, Neurovaskuläre AG Recruiting
Gießen, Germany, 35392
Contact: Manfred Kaps, Prof. MD     0049 641-98540     manfred.kaps@neuro.med.uni-giessen.de    
Sub-Investigator: Christian Tanislav, MD            
Augustahospital AnholT GmbH, Abt. Neurologie Recruiting
Isselburg, Germany, 46419
Contact: Michael Haupts, Prof. MD     0049 2874 46 430     m.haupts@augustahospital.de    
Sub-Investigator: Christian Haug, MD            
Universität Münster, Klinik & Poliklinik für Neurologie Recruiting
Münster, Germany, 48149
Contact: Bernd Ringelstein, Prof. MD     0049 25183 48172     ringels@uni-muenster.de    
Sub-Investigator: Thomas Duning, MD            
Universität Rostock, Zentrum für Nervenheilkunde Recruiting
Rostock, Germany, 18147
Contact: Uwe Zettl, Prof. MD     0049 381494 9517     uwe.zettl@med.uni-rostock.de    
Sub-Investigator: Alexander Winkelmann, MD            
Krankenhaus der Bamherzigen Brüder Trier, Neurologische Klinik Recruiting
Trier, Germany, 54292
Contact: Matthias Maschke, Prof. MD     0049 651 2082741     m.maschke@bk-trier.de    
Sub-Investigator: Christoph Klawe, MD            
Universitätsklinikum Ulm, Klinik für Neurologie Recruiting
Ulm, Germany, 89081
Contact: Hayrettin Tumani, MD     +49 731177 ext 1207     hayrettin.tumani@uni-ulm.de    
Sub-Investigator: Simonetta Niendorf, MD            
Sub-Investigator: Florian Lauda, MD            
Universitätsklinik Würzburg, Neurologische Klinik Recruiting
Würzburg, Germany, 97080
Contact: Christoph Kleinschnitz, MD     0049 93120123488     christoph.kleinschnitz@mail.uni-wuerzburg.de    
Sub-Investigator: Peter Kraft, MD            
Sub-Investigator: Gesa Weise, MD            
Sponsors and Collaborators
University of Rostock
Investigators
Principal Investigator: Arndt Rolfs, MD University of Rostock, Albrecht-Kossel-Institute for Neuroregeneration
  More Information

Publications:

Responsible Party: Prof. Dr. Arndt Rolfs, Prof. Dr. med., University of Rostock
ClinicalTrials.gov Identifier: NCT01271699     History of Changes
Other Study ID Numbers: MS01/2011
Study First Received: January 6, 2011
Last Updated: March 15, 2013
Health Authority: Germany: Ethics Commission

Keywords provided by University of Rostock:
Fabry Disease
Fabry´s Disease
Anderson-Fabry Disease
Multiple Sclerosis

Additional relevant MeSH terms:
Fabry Disease
Multiple Sclerosis
Sclerosis
Sphingolipidoses
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
 Metabolism, Inborn Errors
Lipidoses
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on May 19, 2013