ImmunodeficiencyEUMAPNCT03651245
European Alpha-Mannosidosis Participant
An observational study of Immunodeficiency and Skeletal Abnormalities, run by CENTOGENE GmbH Rostock at 19 sites in 2 countries.
Trial summary
International, multicenter, observational, longitudinal monitoring study to investigate the prevalence of Alpha-Mannosidosis in participants at risk for Alpha-Mannosidosis. Read more about this study
- Who is it for?
- Ages 2 months to 18 years
- Conditions the study is for
- Immunodeficiency, Skeletal Abnormalities, Deafness
- How many people
- 667 participants
- Where
- 19 sitesin 2 countries
- Study dates
- 20 Aug 2018to 30 May 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 months to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Participants at risk for Alpha-Mannosidosis
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
19 sites in 2 countries.
19 sites in 2 countries
Germany17 sites
Uniklinik RWTH Aachen Klinik für Kinder- und Jugendmedizin
Aachen, 52074
Charité - Universitätsmedizin Berlin, Leitung Sozialpädiatrisches Zentrum, Klinik für Pädiatrie m.S. Neurologie
Berlin, 13353
Carl-Thiem-Klinikum Cottbus GmbH, Klinik für Kinder und Jugendmedizin
Cottbus, 03049
Universitätsklinikum Essen, Klinik für Hals-Nasen und Ohrenheilkunde
Essen, 45147
Universitätsklinikum Gießen, Zentrum für Kinderheilkunde und Jugendmedizin, Abteilung für Kinderneurologie, Sozialpädiatrie und Epileptologie
Giessen, 35385
Universitätsklinikum Halle Universitätsklinik und Poliklinik für Pädiatrie I
Halle, 06097
UKE - Universitätsklinikum Hamburg-Eppendorf Klinik und Poliklinik für Hals-, Nasen- und Ohrenheilkunde
Hamburg, 20246
Evangelisches Krankenhaus Hamm, Klinik für Kinder-und Jugendmedizin
Hamm, 59063
Medizinische Hochschule Hannover, Deutsches HörZentrum Hannover
Hanover, 30625
Universitätsklinikum Jena, Klinik für Hals-, Nasen- und Ohrenheilkunde
Jena, 07747
Universitätsklinikum Jena, Klinik für Neuropädiatrie
Jena, 07747
UNIVERSITÄTSKLINIKUM LEIPZIG AöR, Klinik und Poliklinik für Hals-, Nasen-, Ohrenheilkunde
Leipzig, 04103
Sozialpädiatrisches Zentrum der HTZ Neuwied gGmbH
Neuwied, 56564
Evangelisches Krankenhaus Oberhausen, Sozialpädiatrisches Zentrum
Oberhausen, 46047
Elblandkliniken Stiftung & Co. KG - Elblandklinkum Riesa Sozialpädiatrisches Zentrum und Frühförderstelle
Riesa, 01589
Klinik für Kinder-und Jungendmedizin des Universitätsklinikums Ulm
Ulm, 89075
Zentrum für Kinder und Jugendliche Sozialpädiatrisches Zentrum (SPZ) im Marien-Hospital
Wesel, 46483
Switzerland2 sites
HNO-Universitätsklinik, Universitätsspital Basel
Basel, 4031
Inselspital Bern Universitätsklinik für Neurologie
Bern, 3010
About this study
Official title: European Alpha-Mannosidosis Participant: An International, Multicenter, Epidemiological Protocol
International, multicenter, observational, longitudinal monitoring study to investigate the prevalence of Alpha-Mannosidosis in participants at risk for Alpha-Mannosidosis.
Read the 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.
- Conditions
- Immunodeficiency, Skeletal Abnormalities, Deafness, Mental Retardation, Gingival Hypertrophy, Facial Dysmorphism
- Keywords
- Alpha-Mannosidosis disease, prevalence
- Medical subject headings
- Immunologic Deficiency Syndromes, Deafness, Intellectual Disability, Gingival Hypertrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Participants with suspicion for Alpha-Mannosidosis | Participants with suspicion for Alpha-Mannosidosis based on their clinical symptoms aged from 2 months to 18 years |
What is being measured
The primary outcome is the main question the study is designed to answer.
Epidemiological analysis of the prevalence of Alpha-Mannosidosis disease in a cohort of patients with suspicion for Alpha-Mannosidosis, based on their clinical symptoms.
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)
Measured: 3 years
Secondary outcomes (1)
Establishment of biomarker/s in MAN2B1 positive cohort.
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.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2018
- Study start20 Aug 2018
- Primary completion30 May 2022
- Study completion30 May 2022
Why it stopped: we will update quickly
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ImmunodeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 667 participants (actual)
Sponsor and investigators
- Lead sponsor
- CENTOGENE GmbH Rostock
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Peter Bauer, Prof. Dr., Study chair, CENTOGENE GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03651245
- Sponsor's protocol ID
- EUMAP-2018
- Acronym
- EUMAP
- Status last verified
- Jun 2022
- First submitted
- 24 Aug 2018
- Last updated
- 13 Jun 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- European Alpha-Mannosidosis Participant: An International, Multicenter, Epidemiological Protocol
- ClinicalTrials.gov ID
- NCT03651245
- Acronym / sponsor ID
- EUMAP / EUMAP-2018
- Conditions
- Immunodeficiency, Skeletal Abnormalities, Deafness, Mental Retardation, Gingival Hypertrophy, Facial Dysmorphism
- Keywords
- Alpha-Mannosidosis disease, prevalence
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: we will update quickly
- Enrolment
- 667 participants (actual)
- Lead sponsor
- CENTOGENE GmbH RostockIndustry (pharma, biotech, devices)
- Study start
- 20 Aug 2018 (actual)
- Primary completion
- 30 May 2022 (actual)
- Study completion
- 30 May 2022 (actual)
- First posted
- 29 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
International, multicenter, observational, longitudinal monitoring study to investigate the prevalence of Alpha-Mannosidosis in participants at risk for Alpha-Mannosidosis.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Participants with suspicion for Alpha-Mannosidosis | – | –Participants with suspicion for Alpha-Mannosidosis based on their clinical symptoms aged from 2 months to 18 years |
Who may qualify
- Ages
- 2 months to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Participants at risk for Alpha-Mannosidosis
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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)
1 secondary outcome
Establishment of biomarker/s in MAN2B1 positive cohort.
Time frame: 3 years
Results and safety
The study was stopped early (reason given: we will update quickly). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jun 2022.
- CENTOGENE is a rare disease company focused on transforming clinical, genetic, and biochemical data into medical solutions for patientsLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Bauer, Prof. Dr. study chair
CENTOGENE GmbH
19 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Immunodeficiency and Skeletal Abnormalities, run by CENTOGENE GmbH Rostock at 19 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in Germany, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: we will update quickly). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jun 2022.