- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00498420
The Natural History of Alpha-Mannosidosis (HUE-MAN)
A Multicenter, Multinational Study That Will Evaluate Clinical and Surrogate Parameters Known to be Affected in Alpha-Mannosidosis Patients
Study Overview
Status
Conditions
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 Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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Prague, Czechia, 12000 Prague
- Department of Pediatrics, Charles University
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Mainz, Germany, 55101
- University of Mainz
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Tromsoe, Norway, N-9038
- Department of Medicine, University of Tromsoe
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Manchester, United Kingdom, M27 4HA
- Willink Biochemical Genetics Unit,. Royal Manchester Children's Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
Study Plan
How is the study designed?
Design Details
- Observational Models: Other
- Time Perspectives: Prospective
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Michael Beck, MD, Children's Hospital, University of Mainz
- Principal Investigator: Ed Wraith, MD, Willink Biochemical Genetics Unit, Royal Manchester Childern's Hospital
- Principal Investigator: Jiri Zeman, MD, Department of Pediatrics, Charles University
- Principal Investigator: Dag Malm, MD, Department of Medicine, University of Tromsoe
Publications and helpful links
General 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.
- Borgwardt 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.
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- rhLAMAN-01
- 2004-2.1.1-10
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Alpha Mannosidosis
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Zymenex A/SEuropean CommissionUnknown
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Zymenex A/SEuropean CommissionCompleted
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CENTOGENE GmbH RostockWithdrawnAlpha-Mannosidase B Deficiency | Lysosomal Alpha B Mannosidosis | Alpha-Mannosidase DeficiencyIndia, Sri Lanka, Germany
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Chiesi Farmaceutici S.p.A.CompletedAlpha-MannosidosisFrance
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Zymenex A/SEuropean CommissionCompletedA Placebo-Controlled Phase 3 Trial of Repeated Lamazym Treatment of Subjects With Alpha-MannosidosisAlpha-MannosidosisDenmark, United Kingdom, France, Germany, Poland
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Chiesi Farmaceutici S.p.A.Not yet recruiting
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Chiesi Farmaceutici S.p.A.CromsourceCompletedAlpha-MannosidosisFrance, Denmark, Austria, Germany, Italy
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Chiesi Farmaceutici S.p.A.Withdrawn
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Chiesi Farmaceutici S.p.A.Completed