Biomarker for Metachromatic Leukodystrophy Disease (BioMeta)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by University of Rostock
Sponsor:
Collaborator:
Centogene AG Rostock
Information provided by (Responsible Party):
Prof. Dr. Arndt Rolfs, University of Rostock
ClinicalTrials.gov Identifier:
NCT01536327
First received: February 21, 2012
Last updated: October 7, 2014
Last verified: October 2014
  Purpose

Development of a new MS-based biomarker for the early and sensitive diagnosis of metachromatic leukodystrophy disease from plasma. Testing for clinical robustness, specificity and long-term stability of the biomarker.


Condition
Leukodystrophy, Metachromatic
Hereditary Central Nervous System Demyelinating Diseases
Brain Diseases, Metabolic, Inborn
Sphingolipidoses
Lysosomal Storage Diseases, Nervous System

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

Resource links provided by NLM:


Further study details as provided by University of Rostock:

Primary Outcome Measures:
  • Development of a new MS-based biomarker for the early and sensitive diagnosis of Metachromatic Leukodystrophy disease from plasma and saliva [ Time Frame: 24 month ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Testing for clinical robustness, specificity and long-term stability of the biomarker [ Time Frame: 24 month ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

For the development of the new biomarkers using the technique of Mass-spectometry 10ml EDTA blood, sputum tube and a dry blood spot filter card are taken. To proof the correct diagnosis in those patients where up to the enrollment in the study no genetic testing has been done, sequencing 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: 80
Study Start Date: September 2011
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts
Observation
Patients with a diagnosis of Metachromatic Leukodystrophy disease based upon biochemical and/or genetic criteria or profound suspicion for Metachromatic Leukodystrophy disease

Detailed Description:

Metachromatic leukodystrophy (MLD) is one of a group of genetic disorders called the leukodystrophies. These diseases impair the growth or development of the myelin sheath, the fatty covering that acts as an insulator around nerve fibers. Myelin, which lends its color to the white matter of the brain, is a complex substance made up of varying lipids (75%) and proteins (25%). The leukodystrophies are caused by genetic defects in myelin production or metabolization of the compounds of the myelin sheath. Each of the leukodystrophies is the result of a defect in the gene that controls one (and only one) of the enzymes responsible for creating or degrading a part of the myelin. MLD is caused by a deficiency of the enzyme arylsulfatase A. MLD is one of several lipid storage diseases, which results in the toxic build-up of fatty materials (lipids) in cells in the nervous system, liver, and kidneys. There are three forms of MLD: late infantile, juvenile, and adult. Onset of the late infantile form (the most common MLD) is typically between 12 and 20 months following birth. Affected children have difficulty walking after the first year of life. Symptoms include muscle wasting and weakness, muscle rigidity, developmental delays, progressive loss of vision leading to blindness, convulsions, impaired swallowing, paralysis, and dementia. Children may become comatose. Most children with this form of MLD die by age 5. The juvenile form of MLD (between 3-10 years of age) usually begins with impaired school performance, mental deterioration, and dementia and then develop symptoms similar to the infantile form but with slower progression. The adult form commonly begins after age 16 as a psychiatric disorder or progressive dementia. Symptoms include impaired concentration, ataxia, seizures, dementia, and tremor.

New methods, like mass-spectrometry give a good chance to characterize specific metabolic alterations in the blood (plasma) of affected patients that allow to diagnose in the future the disease earlier, with a higher sensitivity and specificity. Therefore it is the goal of the study to develop new biochemical markers from the plasma of the affected patients helping to benefit other patients by an early diagnose and thereby with an earlier treatment.

  Eligibility

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

Patients with a diagnosis of Metachromatic Leukodystrophy disease or profound suspicion for Metachromatic Leukodystrophy 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 Metachromatic Leukodystrophy (MLD) based upon biochemical and/or genetic criteria or profound suspicion for Metachromatic Leukodystrophy disease.

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

  • Positive family anamnesis for MLD
  • Neurologic symptoms of unknown origin: peripheral neuropathy, clumsiness, choreatiform movements, spastic quadriplegia, loss of ambulation, bulbar dysfunction/paresis, dysphagia, seizure disorders
  • Psychiatric symptoms of unknown origin: mental regression, emotional liability, disorganized thinking or hallucinations/delusions Muscle symptoms of unknown origin: muscle weakness

Exclusion Criteria:

  • No written informed consent will be obtained from the patient or their parents before any study related procedures
  • No diagnosis of MLD or no valid criteria for high-grade suspicion of MLD
  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: NCT01536327

Contacts
Contact: Arndt Rolfs, Prof. +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         
Germany
University of Rostock, Albrecht-Kossel-Institute for Neuroregeneration Recruiting
Rostock, Germany, 18147
Contact: Susanne Zielke    +49 381 494 ext 4739    susanne.zielke@med.uni-rostock.de   
Principal Investigator: Arndt Rolfs, Prof.         
India
NIRMAN, University of Mumbai Recruiting
Mumbai, India, 400705
Contact: Anil Jalan, MD       jalananil@yahoo.com   
Principal Investigator: Anil Jalan, MD         
Sponsors and Collaborators
University of Rostock
Centogene AG Rostock
Investigators
Principal Investigator: Arndt Rolfs, Prof. University of Rostock, Albrecht-Kossel-Institute for Neuroregeneration
  More Information

Additional Information:
No publications provided

Responsible Party: Prof. Dr. Arndt Rolfs, Prof. Dr. med., University of Rostock
ClinicalTrials.gov Identifier: NCT01536327     History of Changes
Other Study ID Numbers: BMLE11/2011
Study First Received: February 21, 2012
Last Updated: October 7, 2014
Health Authority: Germany: Ethics Commission

Keywords provided by University of Rostock:
Metachromatic Leukodystrophy
Demyelinating Diseases

Additional relevant MeSH terms:
Lysosomal Storage Diseases
Lysosomal Storage Diseases, Nervous System
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Demyelinating Diseases
Hereditary Central Nervous System Demyelinating Diseases
Leukodystrophy, Metachromatic
Lipid Metabolism Disorders
Metabolic Diseases
Nervous System Diseases
Sphingolipidoses
Central Nervous System Diseases
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Leukoencephalopathies
Lipid Metabolism, Inborn Errors
Lipidoses
Metabolism, Inborn Errors
Neurodegenerative Diseases
Sulfatidosis

ClinicalTrials.gov processed this record on October 20, 2014