The Natural History of Alpha-Mannosidosis (HUE-MAN)

This study has been completed.
Sponsor:
Collaborator:
European Commission
Information provided by:
Zymenex A/S
ClinicalTrials.gov Identifier:
NCT00498420
First received: July 9, 2007
Last updated: February 5, 2010
Last verified: February 2010
  Purpose

The natural history study of the rare lysosomal disease alpha-mannosidosis will answer the question; why the rare disease develops as it does?


Condition
Alpha Mannosidosis

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: A Multicenter, Multinational Study That Will Evaluate Clinical and Surrogate Parameters Known to be Affected in Alpha-Mannosidosis Patients

Resource links provided by NLM:


Further study details as provided by Zymenex A/S:

Biospecimen Retention:   Samples With DNA

Blood


Enrollment: 45
Study Start Date: May 2007
Study Completion Date: November 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
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

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

To be eligible to proceed, each subject must meet all inclusion and exclusion criteria during the screening periode.

Criteria

Inclusion Criteria:

  1. The patient (or patient's legal guardian) must provide written informed consent prior to performing any survey-related procedures.
  2. The patient must have a documented diagnosis of Alpha Mannosidosis, confirmed at screening by measurable clinical signs and symptoms of Alpha Mannosidosis
  3. Documented deficiency of serum or leukocyte acid alpha-mannosidase enzyme activity level

Exclusion Criteria:

  1. History of bone marrow transplantation.
  2. Use of an investigational drug within 30 days prior to study enrollment.
  3. Known medical condition, serious intercurrent illness, or other extenuating circumstance that may significantly decrease study compliance.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00498420

Locations
Czech Republic
Department of Pediatrics, Charles University
Prague, Czech Republic, 12000 Prague
Germany
University of Mainz
Mainz, Germany, 55101
Norway
Department of Medicine, University of Tromsoe
Tromsoe, Norway, N-9038
United Kingdom
Willink Biochemical Genetics Unit,. Royal Manchester Children's Hospital
Manchester, United Kingdom, M27 4HA
Sponsors and Collaborators
Zymenex A/S
European Commission
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
  More Information

Additional Information:
No publications provided by Zymenex A/S

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Christian Friis, Zymenex
ClinicalTrials.gov Identifier: NCT00498420     History of Changes
Other Study ID Numbers: rhLAMAN-01, 2004-2.1.1-10
Study First Received: July 9, 2007
Last Updated: February 5, 2010
Health Authority: Germany: Ethics Commission
United Kingdom: Research Ethics Committee
Czech Republic: Ethics Committee
Norway:National Committee for Medical and Health Research Ethics

Keywords provided by Zymenex A/S:
HUE-MAN
Rare disorder
Hepatosplenomegaly
Dysostosis

Additional relevant MeSH terms:
Alpha-Mannosidosis
Mannosidase Deficiency Diseases
Carbohydrate Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Metabolic Diseases
Metabolism, Inborn Errors

ClinicalTrials.gov processed this record on October 23, 2014