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European Alpha-Mannosidosis Participant (EUMAP)

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ClinicalTrials.gov Identifier: NCT03651245
Recruitment Status : Recruiting
First Posted : August 29, 2018
Last Update Posted : July 7, 2020
Sponsor:
Information provided by (Responsible Party):
Centogene AG Rostock

Brief Summary:
International, multicenter, observational, longitudinal monitoring study to investigate the prevalence of Alpha-Mannosidosis in participants at risk for Alpha-Mannosidosis.

Condition or disease
Immunodeficiency Skeletal Abnormalities Deafness Mental Retardation Gingival Hypertrophy Facial Dysmorphism

Detailed Description:

Alpha-Mannosidosis is a lysosomal storage disorder of the Glycoprotein family of diseases and is closely related to Mucopolysaccharidoses.It 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 (hydrocephalus); hearing loss; and a clouding of the lens of the eye (cataract).

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. 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.

Modern methods, as DBS based mass-spectrometry give a great opportunity to

  • Simplify the diagnostic process
  • Simplify the logistics
  • Increases stability and reproducibility
  • Characterize specific metabolic alterations in the blood of affected patients that allow diagnosing the disease earlier, with a higher sensitivity and specificity.

A more specific diagnosis that permits earlier detection of the disease, as well as assessment of the disease activity and progression, would also permit improved chances for earlier treatment of those patients suffering from the disease.

It is the goal of this international, multicentre, epidemiological study to explore and analyse the prevalence of Alpha-Mannosidosis disease in a cohort of 1.000 patients with a suspicion of Alpha-Mannosidosis disease, based on the patient's clinical symptoms.

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Study Type : Observational
Estimated Enrollment : 1000 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: European Alpha-Mannosidosis Participant: An International, Multicenter, Epidemiological Protocol
Actual Study Start Date : August 20, 2018
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020


Group/Cohort
Participants with suspicion for Alpha-Mannosidosis
Participants with suspicion for Alpha-Mannosidosis based on their clinical symptoms aged from 2 months to 18 years



Primary Outcome Measures :
  1. Epidemiological analysis of the prevalence of Alpha-Mannosidosis disease in a cohort of patients with suspicion for Alpha-Mannosidosis, based on their clinical symptoms. [ Time Frame: 3 years ]
    Number of identified Alpha-Mannosidosis patients, showing a mutation/pathogenic variant in the MAN2B1-Gene, within a cohort of 1000 suspected cases using respective patient's dry-blood sample for confirmatory genetic testing (NGS-based sequencing of MAN2B1-gene)


Secondary Outcome Measures :
  1. Establishment of biomarker/s in MAN2B1 positive cohort. [ Time Frame: 3 years ]
    Alpha-Mannosidosis-positive samples will be validated for the identification of potential biomarkers (based on MS/MS-Tandem spectroscopy) and compared with the merged control samples in order establish a disease-specific biomarker.


Biospecimen Retention:   Samples With DNA
Blood sample applied on the Dry Blood Spot (DBS) Filtercard (Centocard®)


Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   2 Months to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Participants at risk for Alpha-Mannosidosis
Criteria

Inclusion Criteria:

  • Informed consent is obtained from the participant's parent/legal guardian
  • The participant is aged between 2 months and 18 years of age
  • The participant has a family history of Alpha-Mannosidosis or is at risk for Alpha-Mannosidosis according to one or more of the following symptoms: recurrent infections, skeletal abnormalities, hearing impairment-deafness, progressive neurological symptoms, impairment of mental functions, gingival hypertrophy, dysmorphic facial features, motoric disturbances of no obvious etiology

Exclusion Criteria:

  • Informed consent is not provided by the partici-pant's parent/legal guardian
  • The participant is younger than 2 months or older than 18 years
  • The participant has no family history of Alpha-Mannosidosis and is not at risk for Alpha-Mannosidosis (represents none of the following symptoms): recurrent infections, skeletal abnormalities, hearing impairment-deafness, progressive neurological symptoms, impairment of mental functions, gingival hypertrophy, dysmorphic facial features, motoric disturbances of no obvious etiology

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): NCT03651245


Contacts
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Contact: Volha Skrahina, PhD +49 (0)38180113594 volha.skrahina@centogene.com
Contact: Susanne Zielke +49 (0)38180113667 Susanne.Zielke@centogene.com

Locations
Show Show 21 study locations
Sponsors and Collaborators
Centogene AG Rostock
Investigators
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Principal Investigator: Arndt Rolfs, Prof. Dr. Centogene AG Rostock
Additional Information:
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Responsible Party: Centogene AG Rostock
ClinicalTrials.gov Identifier: NCT03651245    
Other Study ID Numbers: EUMAP-2018
First Posted: August 29, 2018    Key Record Dates
Last Update Posted: July 7, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Centogene AG Rostock:
Alpha-Mannosidosis disease
prevalence
Additional relevant MeSH terms:
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Gingival Hypertrophy
Deafness
Intellectual Disability
Mannosidase Deficiency Diseases
alpha-Mannosidosis
Hypertrophy
Pathological Conditions, Anatomical
Hearing Loss
Hearing Disorders
Ear Diseases
Otorhinolaryngologic Diseases
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Neurobehavioral Manifestations
Neurodevelopmental Disorders
Mental Disorders
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Metabolic Diseases
Gingival Overgrowth
Gingival Diseases
Periodontal Diseases
Mouth Diseases
Stomatognathic Diseases