Alpha MannosidosisHUE-MANNCT00498420
The Natural History of Alpha-Mannosidosis
An observational study of Alpha Mannosidosis, run by Zymenex A/S at 4 sites in 4 countries.
Trial summary
The natural history study of the rare lysosomal disease alpha-mannosidosis will answer the question; why the rare disease develops as it does? Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Alpha Mannosidosis
- How many people
- 45 participants
- Where
- 4 sitesin 4 countries
- Study dates
- May 2007to Nov 2009
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: To be eligible to proceed, each subject must meet all inclusion and exclusion criteria during the screening periode.
Who may be able to join
- The patient (or patient's legal guardian) must provide written informed consent prior to performing any survey-related procedures.
- The patient must have a documented diagnosis of Alpha Mannosidosis, confirmed at screening by measurable clinical signs and symptoms of Alpha Mannosidosis
- Documented deficiency of serum or leukocyte acid alpha-mannosidase enzyme activity level
Who cannot join
- History of bone marrow transplantation.
- Use of an investigational drug within 30 days prior to study enrollment.
- Known medical condition, serious intercurrent illness, or other extenuating circumstance that may significantly decrease study compliance.
Trial locations and contacts
4 sites in 4 countries.
4 sites in 4 countries
Czechia1 site
Department of Pediatrics, Charles University
Prague, 12000 Prague
United Kingdom1 site
Willink Biochemical Genetics Unit,. Royal Manchester Children's Hospital
Manchester, M27 4HA
About this study
Official title: A Multicenter, Multinational Study That Will Evaluate Clinical and Surrogate Parameters Known to be Affected in Alpha-Mannosidosis Patients
The natural history study of the rare lysosomal disease alpha-mannosidosis will answer the question; why the rare disease develops as it does?
Read the detailed description
Definition:
Human alpha-mannosidosis is a rare genetic disorder, caused by the lack of lysosomal alpha-mannosidase, resulting in mental retardation, skeletal changes, hearing loss and recurrent infections. The lack of alpha-mannosidase causes a disorder of glycoprotein catabolism associated with abnormal levels and excretion of small mannose-rich oligosaccharides.
Prevalence:
Alpha-mannosidosis belongs to a group of lysosomal storage disorders that includes more than 50 different diseases, with a cumulative frequency of about 1:10.000 world wide. The incidence of alpha-mannosidase disease has been estimated to be 1 in 500.000 (Australian and Norwegian study). The disease is not specific to any ethnic group.
Etiology and Pathogenesis:
Lysosomal alpha-mannosidase (LAMAN), in the following called mannosidase, is an enzyme that cleaves alpha-mannosidic linkages during the ordered degradation of oligosaccharides. Only after degradation, can the sugars leave the lysosomes, the cell and later the body. The deficiency in mannosidase activity causes a block in the degradation of glycoproteins resulting in lysosomal accumulation of mannose-rich oligosaccharide chains. Consequently, these sugars accumulate in the lysosomes as they are too large to leave. Finally, the lysosomes increase in size, producing vacuoles and impaired cellular function is induced by an unknown mechanism.
Clinical Findings:
Affected children are usually born apparently normal and their condition worsens progressively without any possible treatment available to prevent this evolution. The clinical findings in alpha-mannosidosis include a broad range of symptoms, from an early lethal form to less symptomatic, chronic forms often initially diagnosed in childhood. Alpha-mannosidosis is frequently associated with corneal opacities, aseptic destructive arthritis, metabolic myopathy and immune deficiency. In the past alpha-mannosidosis was classified into two forms. A more severe infantile (type 1) phenotype that include rapid, progressive mental retardation; hepatosplenomegaly; severe dysostosis multiplex; and often death between 3 and 12 years of age. The juvenile-adult phenotype (type 2) is characterized by a milder and more slowly progressive course with survival into adulthood. The distinctions are not absolute, and symptoms and lethality may vary. In affected children that are born healthy, there is a window of opportunity for a therapy initiated at an early age to contribute to normal development and the prevention of other disease related complications.
Study objectives:
To assess the short-term, natural history of subjects diagnosed with Alpha-Mannosidosis To establish the range and diversity of clinical symptomatology To evaluate short term (24 months) changes in disease parameters
- Conditions
- Alpha Mannosidosis
- Keywords
- HUE-MAN, Rare disorder, Hepatosplenomegaly, Dysostosis
- Medical subject headings
- alpha-Mannosidosis, Rare Diseases, Dysostoses
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2007 (estimated)
- Study startMay 2007
- Primary completionSep 2009
- Study completionNov 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Alpha MannosidosisStudies 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
- Other
- Time perspective
- Prospective
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Zymenex A/S
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- European Commission
- Responsible party
- Sponsor
- Investigators
- Michael Beck, MD, Principal investigator, Children's Hospital, University of MainzEd Wraith, MD, Principal investigator, Willink Biochemical Genetics Unit, Royal Manchester Childern's HospitalJiri Zeman, MD, Principal investigator, Department of Pediatrics, Charles UniversityDag Malm, MD, Principal investigator, Department of Medicine, University of Tromsoe
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00498420
- Sponsor's protocol ID
- rhLAMAN-01
- Other IDs
- 2004-2.1.1-10
- Acronym
- HUE-MAN
- Status last verified
- Jul 2020
- First submitted
- 9 Jul 2007
- Last updated
- 3 Aug 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
Beck M, Olsen KJ, Wraith JE, Zeman J, Michalski JC, Saftig P, Fogh J, Malm D. Natural history of alpha mannosidosis a longitudinal study. Orphanet J Rare Dis. 2013 Jun 20;8:88. doi: 10.1186/1750-1172-8-88.
PubMed 23786919Borgwardt L, Stensland HM, Olsen KJ, Wibrand F, Klenow HB, Beck M, Amraoui Y, Arash L, Fogh J, Nilssen O, Dali CI, Lund AM. Alpha-mannosidosis: correlation between phenotype, genotype and mutant MAN2B1 subcellular localisation. Orphanet J Rare Dis. 2015 Jun 6;10:70. doi: 10.1186/s13023-015-0286-x.
PubMed 26048034
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Multinational Study That Will Evaluate Clinical and Surrogate Parameters Known to be Affected in Alpha-Mannosidosis Patients
- ClinicalTrials.gov ID
- NCT00498420
- Acronym / sponsor ID
- HUE-MAN / rhLAMAN-01
- Conditions
- Alpha Mannosidosis
- Keywords
- HUE-MAN, Rare disorder, Hepatosplenomegaly, Dysostosis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Zymenex A/SIndustry (pharma, biotech, devices)
- Collaborators
- European Commission
- Study start
- May 2007
- Primary completion
- Sep 2009 (actual)
- Study completion
- Nov 2009 (actual)
- First posted
- 10 Jul 2007 (estimated)
- 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.
The natural history study of the rare lysosomal disease alpha-mannosidosis will answer the question; why the rare disease develops as it does?
Detailed description
Definition:
Human alpha-mannosidosis is a rare genetic disorder, caused by the lack of lysosomal alpha-mannosidase, resulting in mental retardation, skeletal changes, hearing loss and recurrent infections. The lack of alpha-mannosidase causes a disorder of glycoprotein catabolism associated with abnormal levels and excretion of small mannose-rich oligosaccharides.
Prevalence:
Alpha-mannosidosis belongs to a group of lysosomal storage disorders that includes more than 50 different diseases, with a cumulative frequency of about 1:10.000 world wide. The incidence of alpha-mannosidase disease has been estimated to be 1 in 500.000 (Australian and Norwegian study). The disease is not specific to any ethnic group.
Etiology and Pathogenesis:
Lysosomal alpha-mannosidase (LAMAN), in the following called mannosidase, is an enzyme that cleaves alpha-mannosidic linkages during the ordered degradation of oligosaccharides. Only after degradation, can the sugars leave the lysosomes, the cell and later the body. The deficiency in mannosidase activity causes a block in the degradation of glycoproteins resulting in lysosomal accumulation of mannose-rich oligosaccharide chains. Consequently, these sugars accumulate in the lysosomes as they are too large to leave. Finally, the lysosomes increase in size, producing vacuoles and impaired cellular function is induced by an unknown mechanism.
Clinical Findings:
Affected children are usually born apparently normal and their condition worsens progressively without any possible treatment available to prevent this evolution. The clinical findings in alpha-mannosidosis include a broad range of symptoms, from an early lethal form to less symptomatic, chronic forms often initially diagnosed in childhood. Alpha-mannosidosis is frequently associated with corneal opacities, aseptic destructive arthritis, metabolic myopathy and immune deficiency. In the past alpha-mannosidosis was classified into two forms. A more severe infantile (type 1) phenotype that include rapid, progressive mental retardation; hepatosplenomegaly; severe dysostosis multiplex; and often death between 3 and 12 years of age. The juvenile-adult phenotype (type 2) is characterized by a milder and more slowly progressive course with survival into adulthood. The distinctions are not absolute, and symptoms and lethality may vary. In affected children that are born healthy, there is a window of opportunity for a therapy initiated at an early age to contribute to normal development and the prevention of other disease related complications.
Study objectives:
To assess the short-term, natural history of subjects diagnosed with Alpha-Mannosidosis To establish the range and diversity of clinical symptomatology To evaluate short term (24 months) changes in disease parameters
Study design
- Observational model
- Other
- Time perspective
- Prospective
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- To be eligible to proceed, each subject must meet all inclusion and exclusion criteria during the screening periode.
Key inclusion criteria (3 listed)
- The patient (or patient's legal guardian) must provide written informed consent prior to performing any survey-related procedures.
- The patient must have a documented diagnosis of Alpha Mannosidosis, confirmed at screening by measurable clinical signs and symptoms of Alpha Mannosidosis
- Documented deficiency of serum or leukocyte acid alpha-mannosidase enzyme activity level
Key exclusion criteria (3 listed)
- History of bone marrow transplantation.
- Use of an investigational drug within 30 days prior to study enrollment.
- Known medical condition, serious intercurrent illness, or other extenuating circumstance that may significantly decrease study compliance.
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
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2020.
- Results publication: PubMed 23786919Beck M, Olsen KJ, Wraith JE, Zeman J, Michalski JC, Saftig P, Fogh J, Malm D. Natural history of alpha mannosidosis a longitudinal study. Orphanet J Rare Dis. 2013 Jun 20;8:88. doi: 10.1186/1750-1172-8-88.
- Results publication: PubMed 26048034Borgwardt L, Stensland HM, Olsen KJ, Wibrand F, Klenow HB, Beck M, Amraoui Y, Arash L, Fogh J, Nilssen O, Dali CI, Lund AM. Alpha-mannosidosis: correlation between phenotype, genotype and mutant MAN2B1 subcellular localisation. Orphanet J Rare Dis. 2015 Jun 6;10:70. doi: 10.1186/s13023-015-0286-x.
- These websites are dedicated to the HUE-MAN projectLink provided by the sponsor.
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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.
Michael Beck, MD principal investigator
Children's Hospital, University of Mainz
Ed Wraith, MD principal investigator
Willink Biochemical Genetics Unit, Royal Manchester Childern's Hospital
Jiri Zeman, MD principal investigator
Department of Pediatrics, Charles University
4 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Alpha Mannosidosis, run by Zymenex A/S at 4 sites in 4 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: finished, as of the sponsor's last update on 3 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Czechia, Germany, Norway, United Kingdom. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00498420, which also lists 2 linked publications.
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 3 Aug 2020.