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Biomarker for Mannosidosis Disease (BioMannosidosis) (BioMannosido)

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ClinicalTrials.gov Identifier: NCT03264040
Recruitment Status : Recruiting
First Posted : August 28, 2017
Last Update Posted : September 17, 2019
Sponsor:
Information provided by (Responsible Party):
Centogene AG Rostock

Tracking Information
First Submitted Date August 24, 2017
First Posted Date August 28, 2017
Last Update Posted Date September 17, 2019
Actual Study Start Date August 20, 2018
Estimated Primary Completion Date August 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: January 8, 2019)
Development of a new MS-based biomarker for the early and sensitive diagno-sis of Mannosidosis disease from blood (plasma) [ Time Frame: 24 months ]
New methods, like mass-spectrometry give a good chance to characterize specific metabolic alterations in the blood of affected patients that allow diagnosing in the future the disease earlier, with a higher sensitivity and specificity.
Original Primary Outcome Measures
 (submitted: August 24, 2017)
The diagnosis of alpha Mannosidosis measured by sequencing of alpha Mannosidosis [ Time Frame: 36 months ]
Change History Complete list of historical versions of study NCT03264040 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: January 8, 2019)
Testing for clinical robustness, specificity and long-term stability of the bi-omarker [ Time Frame: 36 months ]
the goal of the study to identify and validate a new biochemical marker from the blood of the affected patients helping to benefit other patients by an early diagnose and thereby with an earlier treatment.
Original Secondary Outcome Measures
 (submitted: August 24, 2017)
Number of correct identified patients with alpha Mannosidosis [ Time Frame: 36 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Biomarker for Mannosidosis Disease (BioMannosidosis)
Official Title Biomarker for Mannosidosis Disease - An International, Multicenter, Epidemiological Protocol
Brief Summary Development of a new MS-based biomarker for the early and sensitive diagnosis of Mannosidosis disease from blood (plasma)
Detailed Description

Alpha-Mannosidosis is a rare lysosomal storage disorder of the Glycoprotein family of diseases and is closely related to Mucopolysaccharidoses.

Alpha-Mannosidosis was first described by Dr Oekerman, from Lund in Sweden in 1967. There is another variant known as Beta-Mannosidosis, which is extremely rare and has produced a wide range of clinical abnormalities in the few patients described with this disorder.

A Alpha-Mannosidosis is a rare inherited disorder that causes problems in many organs and tissues of the body. Affected individuals may have intellectual disability, distinctive facial features, and skeletal abnormalities. Characteristic facial features can include a large head, prominent forehead, low hairline, rounded eyebrows, large ears, flattened bridge of the nose, protruding jaw, widely spaced teeth, overgrown gums, and large tongue. The skeletal abnormalities that can occur in this disorder include reduced bone density (osteopenia), thickening of the bones at the top of the skull (calvaria), deformations of the bones in the spine (vertebrae), bowed legs or knock knees, and deterioration of the bones and joints.

Affected individuals may also experience difficulty in coordinating movements (ataxia); muscle weakness (myopathy); delay in developing motor skills such as sitting and walking; speech impairments; increased risk of infections; enlargement of the liver and spleen (hepatosplenomegaly); a buildup of fluid in the brain (hydrocepha-lus); hearing loss; and a clouding of the lens of the eye (cataract). Some people with Alpha-Mannosidosis experience psychiatric symptoms such as depression, anxiety, or hallucinations; episodes of psychiatric disturbance may be triggered by stressors such as having undergone surgery, emotional upset, or changes in routine.

The signs and symptoms of Alpha-Mannosidosis can range from mild to severe. The disorder may appear in infancy with rapid progression and severe neurological deterioration. Individuals with this early-onset form of Alpha-Mannosidosis often do not survive past childhood. In the most severe cases, an affected fetus may die before birth. Other individuals with Alpha-Mannosidosis experience milder signs and symptoms that appear later and progress more slowly. People with later-onset alpha-mannosidosis may survive into their fifties. The mildest cases may be detected only through laboratory testing and result in few if any symptoms.

Alpha-mannosidosis is estimated to occur in approximately 1 in 500,000 people worldwide.

Mutations in the MAN2B1 gene cause Alpha-Mannosidosis. This gene provides instructions for making the enzyme alpha-mannosidase. This enzyme works in the lysosomes, which are compartments that digest and recycle materials in the cell. With-in lysosomes, the enzyme helps break down complexes of sugar molecules (oligo-saccharides) attached to certain proteins (glycoproteins). In particular, alpha-mannosidase helps break down oligosaccharides containing a sugar molecule called mannose.

Mutations in the MAN2B1 gene interfere with the ability of the alpha-mannosidase enzyme to perform its role in breaking down mannose-containing oligosaccharides. These oligosaccharides accumulate in the lysosomes and cause cells to malfunction and eventually die. Tissues and organs are damaged by the abnormal accumulation of oligosaccharides and the resulting cell death, leading to the characteristic features of Alpha-Mannosidosis.

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 identify and validate a 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.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:

For the development of the new biomarkers using the technique of Mass-spectrometry 2,7 ml EDTA blood or a dry blood spot filter card are taken. To proof the correct Mannosidosis diagnosis in those patients where up to the en-rollment in the study no genetic testing has been done, sequencing of Manno-sidosis disease will be done.

The analyses will be done at the Centogene AG Am Strande 7 18055 Rostock Germany

Sampling Method Probability Sample
Study Population Patients with Mannosidosis disease or high-grade suspicion for Mannosidosis disease
Condition
  • Alpha-Mannosidase B Deficiency
  • Lysosomal Alpha B Mannosidosis
  • Alpha-Mannosidase Deficiency
Intervention Not Provided
Study Groups/Cohorts Observation
Patients with Mannosidosis disease or high-grade suspicion for Mannosidosis disease
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: August 24, 2018)
1000
Original Estimated Enrollment
 (submitted: August 24, 2017)
50
Estimated Study Completion Date August 2021
Estimated Primary Completion Date August 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Informed consent will be obtained from the patient or the parents before any study related procedures.
  • Patients of both genders older than 2 months
  • The patient has a diagnosis of Alpha-Mannosidosis disease or a high grade suspicion for Alpha-Mannosidosis disease
  • High grade suspicion present, if one or more inclusion criteria are valid:

    • Positive family anamnesis for Alpha-Mannosidosis disease
    • rounded eyebrows
    • large head
    • large ears
    • flattened bridge of the nose
    • deformations of the bones in the spine (vertebrae)

Exclusion Criteria:

  • No Informed consent from the patient or the parents before any study related procedures.
  • Patients of both gender younger than 2 months
  • No diagnosis of Alpha-Mannosidosis disease or no valid criteria for profound suspicion of Alpha-Mannosidosis disease
Sex/Gender
Sexes Eligible for Study: All
Ages 2 Months and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers Not Provided
Contacts
Contact: Arndt Rolfs, Prof +4938180113500 ext 500 arndt.rolfs@centogene.com
Listed Location Countries Egypt,   Germany,   India,   Pakistan
Removed Location Countries  
 
Administrative Information
NCT Number NCT03264040
Other Study ID Numbers BMA 06-2018
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party Centogene AG Rostock
Study Sponsor Centogene AG Rostock
Collaborators Not Provided
Investigators
Principal Investigator: Arndt Rolfs, Prof. Centogene AG Rostock
PRS Account Centogene AG Rostock
Verification Date June 2019