Biomarker for GM1/GM2 - Gangliosidoses (BioGM1BioGM2)
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ClinicalTrials.gov Identifier: NCT02298647 |
Recruitment Status
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Recruiting
First Posted
: November 24, 2014
Last Update Posted
: February 6, 2018
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Tracking Information | |||||||||
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First Submitted Date | October 23, 2014 | ||||||||
First Posted Date | November 24, 2014 | ||||||||
Last Update Posted Date | February 6, 2018 | ||||||||
Study Start Date | November 2014 | ||||||||
Estimated Primary Completion Date | November 2019 (Final data collection date for primary outcome measure) | ||||||||
Current Primary Outcome Measures |
Development of a new MS-based biomarker for the early and sensitive diagnosis of GM1/GM2 -gangliosidoses from plasma and saliva using [ Time Frame: 36 month ] | ||||||||
Original Primary Outcome Measures | Same as current | ||||||||
Change History | Complete list of historical versions of study NCT02298647 on ClinicalTrials.gov Archive Site | ||||||||
Current Secondary Outcome Measures |
Testing for clinical robustness, specificity and long-term stability of the biomarker [ Time Frame: 36 month ] | ||||||||
Original Secondary Outcome Measures | Same as current | ||||||||
Current Other Outcome Measures | Not Provided | ||||||||
Original Other Outcome Measures | Not Provided | ||||||||
Descriptive Information | |||||||||
Brief Title | Biomarker for GM1/GM2 - Gangliosidoses | ||||||||
Official Title | Biomarker for GM1/GM2-Gangliosidoses - AN INTERNATIONAL, MULTICENTER, EPIDEMIOLOGICAL PROTOCOL | ||||||||
Brief Summary | Development of a new MS-based biomarker for the early and sensitive diagnosis of metachromatic leukodystrophy disease from plasma and saliva. Testing for clinical robustness, specificity and long-term stability of the biomarker. | ||||||||
Detailed Description | Gangliosides are complex compunds consisting of a glycosphingolipid and a sialic acid and are located at the cell surface where they are responsible for detecting extracellular mole-cules. Gangliosides are mainly located in the nervous system. If gangliosides accumulate pathologically throughout the body this is known as gangliosidoss. There are two main sub-types of gangliosidosis depending on the deficient enzyme, which are known as GM1 and GM2. GM1-Gangliosidosis GM1 gangliosidosis is an autosomal recessive disease. Genetic counselling should be pro-vided to affected families. The disorder is caused by mutations in the GLB1-gene coding for beta-galactosidase. To day, more than 165 mutations have been identified. Deficient enzyme activity leads to toxic accumulation of gangliosides in body tissues, and particularly in the central nervous system (CNS). The disorder is panethnic however the worldwide prevalence is not known. Prevalence at birth is estimated to be approximately 1:100,000 to 200,000 live births. High prevalence has been found in Malta and Brazil, and in the Cypriot and Roma populations. Deficiency of the lysosomal hydrolase, acid β-galactosidase, causes GM1.Three clinical sub-types of GM1 gangliosidosis are recognized, classified by age of onset, as follows:
GM2-Gangliosidosis The GM2 gangliosidosis are a group of lysosomal lipid storage disorders caused by mutations in at least 1 of 3 recessive genes: HEXA, HEXB, and GM2A. Normal products of all 3 genes are required for normal catabolism of the GM2 ganglioside substrate. Deficient activity of these enzymes leads to accumulation of the substrate inside neuronal lysosomes, leading to cell death. The products of the 3 genes are, respectively, the alpha subunits of b-hexosaminidase A (Hex A). Hex A is a dimer and has the structure alpha-beta. β-Hexosaminidase B (Hex B) is a dimer of beta chains. It hydrolyzes GM2 and its neutral asialo derivative GA2. Both subunit precursors acquire the mannose 6-phosphate marker for recognition by lysosomes. Hexosaminidase S (Hex S) is a dimer of alpha chains; it is a normal constituent of plasma and degrades a wide range of glycoconjugates containing β-linked N-acetylhexosaminyl res-idues. With lack of beta-subunits the increased polymerization of alpha subunits leads to the increased formation of Hex S in Tay - Sachs disease. GM2A is a cofactor required for the normal function of Hex A; it´s disruption likewise leads to a reduced function of Hex A. New methods, like mass-spectrometry give a good chance to characterize specific metabolic alterations in the blood (plasma) of affected patients that allow diagnosing in the future the disease earlier, with a higher sensitivity and specificity. Therefore it is the goal of the study to validate this new biochemical marker from the plasma of the affected patients helping to benefit other patients by an early diagnose and thereby with an earlier treatment. Examining saliva samples will allow determining whether measurement is feasible in saliva samples and will further promote early detection of GM1/GM2 disease. |
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Study Type | Observational | ||||||||
Study Design | Observational Model: Cohort Time Perspective: Prospective |
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Target Follow-Up Duration | Not Provided | ||||||||
Biospecimen | Retention: Samples With DNA Description: 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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Sampling Method | Probability Sample | ||||||||
Study Population | Patients with GM1/GM2- Gangliosidoses or high-grade suspicion for GM1/GM2 -Gangliosidoses | ||||||||
Condition |
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Intervention | Not Provided | ||||||||
Study Groups/Cohorts | Observation
Patients with a diagnosis of Gangliosidosis type GM1/GM2 based upon biochemical and/or genetic criteria or profound suspicion for Gangliosidosis type GM1/GM2 |
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Publications * | Not Provided | ||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||
Recruitment Status | Recruiting | ||||||||
Estimated Enrollment |
50 | ||||||||
Original Estimated Enrollment | Same as current | ||||||||
Estimated Study Completion Date | December 2019 | ||||||||
Estimated Primary Completion Date | November 2019 (Final data collection date for primary outcome measure) | ||||||||
Eligibility Criteria | Inclusion Criteria:
High-grade suspicion for GM1 or GM2 pre-sent, if one or more inclusion criteria are valid:
Exclusion Criteria:
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Sex/Gender |
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Ages | 2 Months and older (Child, Adult, Senior) | ||||||||
Accepts Healthy Volunteers | No | ||||||||
Contacts |
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Listed Location Countries | Germany | ||||||||
Removed Location Countries | |||||||||
Administrative Information | |||||||||
NCT Number | NCT02298647 | ||||||||
Other Study ID Numbers | BGM 03-2014 | ||||||||
Has Data Monitoring Committee | Yes | ||||||||
U.S. FDA-regulated Product | Not Provided | ||||||||
IPD Sharing Statement |
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Responsible Party | Prof. Dr. Arndt Rolfs, University of Rostock | ||||||||
Study Sponsor | University of Rostock | ||||||||
Collaborators | Centogene AG Rostock | ||||||||
Investigators |
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PRS Account | University of Rostock | ||||||||
Verification Date | February 2018 |