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Trial record 9 of 31 for:    "mucopolysaccharidosis type III"

Biomarker for Sanfilippo Disease (BioSanfilippo)

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ClinicalTrials.gov Identifier: NCT02298686
Recruitment Status : Recruiting
First Posted : November 24, 2014
Last Update Posted : February 6, 2018
Sponsor:
Collaborator:
Centogene AG Rostock
Information provided by (Responsible Party):
Prof. Dr. Arndt Rolfs, University of Rostock

Brief Summary:
Development of a new MS-based biomarker for the early and sensitive diagnosis of Sanfilippo Type A-B-C-D disease from plasma and saliva. Testing for clinical robustness, specificity and long-term stability of the biomarker.

Condition or disease
Mucopolysaccharidosis Type 3 A Mucopolysaccharidosis Type 3 B Mucopolysaccharidosis Type 3 C Mucopolysaccharidosis Type 3 D Heparan Sulfate Sulfatase Deficiency

Detailed Description:

The Mucopolysaccharidoses (MPS Disorders) are a group of rare genetic disorders caused by the deficiency of one of the lysosomal enzymes, resulting in an inability to metabolize complex carbohydrates (mucopolysaccharides) into simpler molecules. High concentrations of mucopolysaccharides in the cells of the central nervous system, including the brain, cause the neurological and developmental deficits that accompany these disorders. Lysosomal enzymes are found in the lysosome, a very small membrane-contained body (or-ganelle) found in the cytoplasm of most cells. The lysosome is often called the "waste dis-posal plant" of the cell. The accumulation of these large, undegraded mucopolysaccharides in the cells of the body is the cause of a number of physical symptoms and abnormalities. MPS-III (Sanfilippo Syndrome) is one of seven MPS Disorders. It is an inborn error of metab-olism that is transmitted as an autosomal recessive genetic disorder. MPS-lll has been cate-gorized into four subtypes: MPS-III Type A, MPS-III Type B, MPS-III Type C, and MPS-III Type D depending on the gene defect (MPS3A - SGSH gene, MPS3B - NAGLU gene, MPS3C - HGSNAT, MPS3D - GNS gene). All types are associated with some degree of mental deterioration, but the severity depends on the particular type of MPS-lll. Several phys-ical defects may be present, and the severity of these defects varies with the type of MPS-III. In the case of each type of MPS-III, abnormal amounts of a specific, chemically complex molecule is excreted in the urine. The excreted chemical is the same for each of the four types of MPS-III, since the defective gene involves a different step, and thus a different en-zyme, in the deconstruction of the same mucopolysaccharide. By testing for one or another of these enzymes, the variant type may be readily identified.

Symptoms Patients with Sanfilippo Syndrome (MPS Type III) usually appear normal at birth, but mental retardation and developmental delay is usually evident by age 3-5 years. Mental and motor development reaches a peak by 3-6 years of age after which behavioral disturbances and intellectual decline usually occur. However, hyperactivity and irritability may become obvious earlier.

The following symptoms are usually apparent by approximately age 10: neurological deficits and signs, wobbly and erratic gait and difficulty walking (ataxia), hyperactivity (hyperkinetic syndrome), mental retardation, stiff joints, hernias, enlarged liver and/or spleen (hepatosple-nomegaly).Growth is usually minimally affected; the head may be enlarged, and abnormal hairiness (hirsutism) may occur. Mild coarsening of facial features also characterizes this disorder. In some cases deafness may also occur.

All four varieties of MPS-III are autosomal recessive genetic disorders. The gene abnormalities associated with MSS-IIIA, MPS-IIIB, MPS-IIIC and MPS-IIID have been identified. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an af-fected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.


Study Type : Observational
Estimated Enrollment : 50 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Biomarker for Sanfilippo Disease - AN INTERNATIONAL, MULTICENTER, EPIDEMIOLOGICAL PROTOCOL
Study Start Date : November 2014
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : December 2019


Group/Cohort
Observation
Patients with Sanfilippo Type A-B-C-D disease or patients with high-grade suspicion for Sanfilippo Type A-B-C-D disease submitted to the participating centers should be included into the study.



Primary Outcome Measures :
  1. Development of a new MS-based biomarker for the early and sensitive diagnosis of Sanfilippo Type A-B-C-D disease from plasma and saliva [ Time Frame: 36 months ]

Secondary Outcome Measures :
  1. Testing for clinical robustness, specificity and long-term stability of the biomarker [ Time Frame: 36 months ]

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)


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Ages Eligible for Study:   2 Months and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients with Sanfilippo Type A-B-C-D disease or patients with high-grade suspicion for Sanfilippo Type A-B-C-D disease submitted to the participating centers should be included into the study.
Criteria

Inclusion Criteria:

  • Informed consent will be obtained from the patient or the parents before any study related procedures.
  • Patients of both gender older than 2 month
  • The patient has a diagnosis of Sanfilippo Type A-B-C-D disease or high-grade suspicion for Sanfilippo Type A-B-C-D disease

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

  • Positive family anamnesis for Sanfilippo Type A-B-C-D disease
  • Dysostosis multiplex without identifiable cause
  • Splenomegaly without identifiable cause
  • Hepatomegaly without identifiable cause
  • Heparan sulfate excretion in urine
  • CNS involvement without identifiable cause

Exclusion Criteria:

  • No Informed consent from the patient or the parents before any study related pro-cedures
  • Patient of both gender younger than 2 month
  • No diagnosis of Sanfilippo Type A-B-C-D disease or no valid criteria for high-grade suspicion of Sanfilippo Type A-B-C-D disease

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02298686


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
Germany
Albrecht-Kossel-Institute for Neuroregeneration (AKos) Centre for Mental Health Disease University of Rostock Recruiting
Rostock, Germany, 18147
Contact: Arndt Rolfs, Prof.    +49 381 494 ext 9540    arndt.rolfs@med.uni-rostock.de   
Sub-Investigator: Anne Katrin Giese, MD         
Sponsors and Collaborators
University of Rostock
Centogene AG Rostock
Investigators
Principal Investigator: Arndt Rolfs, Prof. University of Rostock, Albrecht-Kossel-Institute for Neuroregeneration

Additional Information:
Responsible Party: Prof. Dr. Arndt Rolfs, Prof. Dr. med., University of Rostock
ClinicalTrials.gov Identifier: NCT02298686     History of Changes
Other Study ID Numbers: BSF01-2014
First Posted: November 24, 2014    Key Record Dates
Last Update Posted: February 6, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Prof. Dr. Arndt Rolfs, University of Rostock:
Inborn Errors of Metabolism
Lysosomal Storage Diseases
Metabolism Errors, Inborn

Additional relevant MeSH terms:
Mucopolysaccharidoses
Mucopolysaccharidosis III
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Mucinoses
Connective Tissue Diseases
Metabolic Diseases