<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03264040</url>
  </required_header>
  <id_info>
    <org_study_id>BMA 06-2018</org_study_id>
    <nct_id>NCT03264040</nct_id>
  </id_info>
  <brief_title>Biomarker for Mannosidosis Disease (BioMannosidosis)</brief_title>
  <acronym>BioMannosido</acronym>
  <official_title>Biomarker for Mannosidosis Disease - An International, Multicenter, Epidemiological Protocol</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>CENTOGENE GmbH Rostock</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>CENTOGENE GmbH Rostock</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Development of a new MS-based biomarker for the early and sensitive diagnosis of Mannosidosis&#xD;
      disease from blood (plasma)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Alpha-Mannosidosis is a rare lysosomal storage disorder of the Glycoprotein family of&#xD;
      diseases and is closely related to Mucopolysaccharidoses.&#xD;
&#xD;
      Alpha-Mannosidosis was first described by Dr Oekerman, from Lund in Sweden in 1967. There is&#xD;
      another variant known as Beta-Mannosidosis, which is extremely rare and has produced a wide&#xD;
      range of clinical abnormalities in the few patients described with this disorder.&#xD;
&#xD;
      A Alpha-Mannosidosis is a rare inherited disorder that causes problems in many organs and&#xD;
      tissues of the body. Affected individuals may have intellectual disability, distinctive&#xD;
      facial features, and skeletal abnormalities. Characteristic facial features can include a&#xD;
      large head, prominent forehead, low hairline, rounded eyebrows, large ears, flattened bridge&#xD;
      of the nose, protruding jaw, widely spaced teeth, overgrown gums, and large tongue. The&#xD;
      skeletal abnormalities that can occur in this disorder include reduced bone density&#xD;
      (osteopenia), thickening of the bones at the top of the skull (calvaria), deformations of the&#xD;
      bones in the spine (vertebrae), bowed legs or knock knees, and deterioration of the bones and&#xD;
      joints.&#xD;
&#xD;
      Affected individuals may also experience difficulty in coordinating movements (ataxia);&#xD;
      muscle weakness (myopathy); delay in developing motor skills such as sitting and walking;&#xD;
      speech impairments; increased risk of infections; enlargement of the liver and spleen&#xD;
      (hepatosplenomegaly); a buildup of fluid in the brain (hydrocepha-lus); hearing loss; and a&#xD;
      clouding of the lens of the eye (cataract). Some people with Alpha-Mannosidosis experience&#xD;
      psychiatric symptoms such as depression, anxiety, or hallucinations; episodes of psychiatric&#xD;
      disturbance may be triggered by stressors such as having undergone surgery, emotional upset,&#xD;
      or changes in routine.&#xD;
&#xD;
      The signs and symptoms of Alpha-Mannosidosis can range from mild to severe. The disorder may&#xD;
      appear in infancy with rapid progression and severe neurological deterioration. Individuals&#xD;
      with this early-onset form of Alpha-Mannosidosis often do not survive past childhood. In the&#xD;
      most severe cases, an affected fetus may die before birth. Other individuals with&#xD;
      Alpha-Mannosidosis experience milder signs and symptoms that appear later and progress more&#xD;
      slowly. People with later-onset alpha-mannosidosis may survive into their fifties. The&#xD;
      mildest cases may be detected only through laboratory testing and result in few if any&#xD;
      symptoms.&#xD;
&#xD;
      Alpha-mannosidosis is estimated to occur in approximately 1 in 500,000 people worldwide.&#xD;
&#xD;
      Mutations in the MAN2B1 gene cause Alpha-Mannosidosis. This gene provides instructions for&#xD;
      making the enzyme alpha-mannosidase. This enzyme works in the lysosomes, which are&#xD;
      compartments that digest and recycle materials in the cell. With-in lysosomes, the enzyme&#xD;
      helps break down complexes of sugar molecules (oligo-saccharides) attached to certain&#xD;
      proteins (glycoproteins). In particular, alpha-mannosidase helps break down oligosaccharides&#xD;
      containing a sugar molecule called mannose.&#xD;
&#xD;
      Mutations in the MAN2B1 gene interfere with the ability of the alpha-mannosidase enzyme to&#xD;
      perform its role in breaking down mannose-containing oligosaccharides. These oligosaccharides&#xD;
      accumulate in the lysosomes and cause cells to malfunction and eventually die. Tissues and&#xD;
      organs are damaged by the abnormal accumulation of oligosaccharides and the resulting cell&#xD;
      death, leading to the characteristic features of Alpha-Mannosidosis.&#xD;
&#xD;
      New methods, like mass-spectrometry give a good chance to characterize specific metabolic&#xD;
      alterations in the blood (plasma) of affected patients that allow diagnosing in the future&#xD;
      the disease earlier, with a higher sensitivity and specificity.&#xD;
&#xD;
      Therefore it is the goal of the study to identify and validate a new biochemical marker from&#xD;
      the plasma of the affected patients helping to benefit other patients by an early diagnose&#xD;
      and thereby with an earlier treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Transition to BioMetabol&#xD;
  </why_stopped>
  <start_date type="Actual">August 20, 2018</start_date>
  <completion_date type="Actual">February 28, 2021</completion_date>
  <primary_completion_date type="Actual">February 28, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Development of a new MS-based biomarker for the early and sensitive diagno-sis of Mannosidosis disease from blood (plasma)</measure>
    <time_frame>24 months</time_frame>
    <description>New methods, like mass-spectrometry give a good chance to characterize specific metabolic alterations in the blood of affected patients that allow diagnosing in the future the disease earlier, with a higher sensitivity and specificity.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Testing for clinical robustness, specificity and long-term stability of the bi-omarker</measure>
    <time_frame>36 months</time_frame>
    <description>the goal of the study to identify and validate a new biochemical marker from the blood of the affected patients helping to benefit other patients by an early diagnose and thereby with an earlier treatment.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">0</enrollment>
  <condition>Alpha-Mannosidase B Deficiency</condition>
  <condition>Lysosomal Alpha B Mannosidosis</condition>
  <condition>Alpha-Mannosidase Deficiency</condition>
  <arm_group>
    <arm_group_label>Observation</arm_group_label>
    <description>Patients with Mannosidosis disease or high-grade suspicion for Mannosidosis disease</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      For the development of the new biomarkers using the technique of Mass-spectrometry 2,7 ml&#xD;
      EDTA blood or a dry blood spot filter card are taken. To proof the correct Mannosidosis&#xD;
      diagnosis in those patients where up to the en-rollment in the study no genetic testing has&#xD;
      been done, sequencing of Manno-sidosis disease will be done.&#xD;
&#xD;
      The analyses will be done at the Centogene AG Am Strande 7 18055 Rostock Germany&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with Mannosidosis disease or high-grade suspicion for Mannosidosis disease&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Informed consent will be obtained from the patient or the parents before any study&#xD;
             related procedures.&#xD;
&#xD;
          -  Patients of both genders older than 2 months&#xD;
&#xD;
          -  The patient has a diagnosis of Alpha-Mannosidosis disease or a high grade suspicion&#xD;
             for Alpha-Mannosidosis disease&#xD;
&#xD;
          -  High grade suspicion present, if one or more inclusion criteria are valid:&#xD;
&#xD;
               -  Positive family anamnesis for Alpha-Mannosidosis disease&#xD;
&#xD;
               -  rounded eyebrows&#xD;
&#xD;
               -  large head&#xD;
&#xD;
               -  large ears&#xD;
&#xD;
               -  flattened bridge of the nose&#xD;
&#xD;
               -  deformations of the bones in the spine (vertebrae)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  No Informed consent from the patient or the parents before any study related&#xD;
             procedures.&#xD;
&#xD;
          -  Patients of both gender younger than 2 months&#xD;
&#xD;
          -  No diagnosis of Alpha-Mannosidosis disease or no valid criteria for profound suspicion&#xD;
             of Alpha-Mannosidosis disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Months</minimum_age>
    <maximum_age>N/A</maximum_age>
  </eligibility>
  <overall_official>
    <last_name>Peter Bauer, Prof.</last_name>
    <role>Study Chair</role>
    <affiliation>Centogene GmbH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Centogene GmbH</name>
      <address>
        <city>Rostock</city>
        <zip>18055</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Navi Mumbai Institute of Research In Mental And Neurological Handicap (NIRMAN)</name>
      <address>
        <city>Mumbai</city>
        <zip>400705</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lady Ridgeway Hospital for Children</name>
      <address>
        <city>Colombo 8</city>
        <zip>00800c</zip>
        <country>Sri Lanka</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>India</country>
    <country>Sri Lanka</country>
  </location_countries>
  <removed_countries>
    <country>Egypt</country>
    <country>Pakistan</country>
  </removed_countries>
  <link>
    <url>http://centogene.com</url>
    <description>Centogene is one of the leading laboratories focusing on genetic testing for rare hereditary disorders. We now offer more than 2200 routine genetic and biochemical tests.</description>
  </link>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>August 24, 2017</study_first_submitted>
  <study_first_submitted_qc>August 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 28, 2017</study_first_posted>
  <last_update_submitted>February 9, 2023</last_update_submitted>
  <last_update_submitted_qc>February 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Mannosidosis</keyword>
  <keyword>Biomarker</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mannosidase Deficiency Diseases</mesh_term>
    <mesh_term>alpha-Mannosidosis</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03264040
org study id: BMA 06-2018
nct id: NCT03264040
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Development of a new MS-based biomarker for the early and sensitive diagnosis of Mannosidosis
      disease from blood (plasma)
Alpha-Mannosidosis is a rare lysosomal storage disorder of the Glycoprotein family of
      diseases and is closely related to Mucopolysaccharidoses.

      Alpha-Mannosidosis was first described by Dr Oekerman, from Lund in Sweden in 1967. There is
      another variant known as Beta-Mannosidosis, which is extremely rare and has produced a wide
      range of clinical abnormalities in the few patients described with this disorder.

      A Alpha-Mannosidosis 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 (hydrocepha-lus); hearing loss; and a
      clouding of the lens of the eye (cataract). Some people with Alpha-Mannosidosis experience
      psychiatric symptoms such as depression, anxiety, or hallucinations; episodes of psychiatric
      disturbance may be triggered by stressors such as having undergone surgery, emotional upset,
      or changes in routine.

      The signs and symptoms of Alpha-Mannosidosis can range from mild to severe. The disorder may
      appear in infancy with rapid progression and severe neurological deterioration. Individuals
      with this early-onset form of Alpha-Mannosidosis often do not survive past childhood. In the
      most severe cases, an affected fetus may die before birth. Other individuals with
      Alpha-Mannosidosis experience milder signs and symptoms that appear later and progress more
      slowly. People with later-onset alpha-mannosidosis may survive into their fifties. The
      mildest cases may be detected only through laboratory testing and result in few if any
      symptoms.

      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. This enzyme works in the lysosomes, which are
      compartments that digest and recycle materials in the cell. With-in lysosomes, the enzyme
      helps break down complexes of sugar molecules (oligo-saccharides) attached to certain
      proteins (glycoproteins). In particular, alpha-mannosidase helps break down oligosaccharides
      containing a sugar molecule called mannose.

      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.

      New methods, like mass-spectrometry give a good chance to characterize specific metabolic
      alterations in the blood (plasma) of affected patients that allow diagnosing in the future
      the disease earlier, with a higher sensitivity and specificity.

      Therefore it is the goal of the study to identify and validate a new biochemical marker from
      the plasma of the affected patients helping to benefit other patients by an early diagnose
      and thereby with an earlier treatment.
observational model: Cohort
time perspective: Prospective
measure: Development of a new MS-based biomarker for the early and sensitive diagno-sis of Mannosidosis disease from blood (plasma)
time frame: 24 months
description: New methods, like mass-spectrometry give a good chance to characterize specific metabolic alterations in the blood of affected patients that allow diagnosing in the future the disease earlier, with a higher sensitivity and specificity.
measure: Testing for clinical robustness, specificity and long-term stability of the bi-omarker
time frame: 36 months
description: the goal of the study to identify and validate a new biochemical marker from the blood of the affected patients helping to benefit other patients by an early diagnose and thereby with an earlier treatment.
arm group label: Observation
description: Patients with Mannosidosis disease or high-grade suspicion for Mannosidosis disease
For the development of the new biomarkers using the technique of Mass-spectrometry 2,7 ml
      EDTA blood or a dry blood spot filter card are taken. To proof the correct Mannosidosis
      diagnosis in those patients where up to the en-rollment in the study no genetic testing has
      been done, sequencing of Manno-sidosis disease will be done.

      The analyses will be done at the Centogene AG Am Strande 7 18055 Rostock Germany
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 2 Months
maximum age: N/A
last name: Peter Bauer, Prof.
role: Study Chair
affiliation: Centogene GmbH
facility: 
facility: 
facility: 
country: Germany
country: India
country: Sri Lanka
country: Egypt
country: Pakistan
url: http://centogene.com
description: Centogene is one of the leading laboratories focusing on genetic testing for rare hereditary disorders. We now offer more than 2200 routine genetic and biochemical tests.
responsible party type: Sponsor
mesh term: Mannosidase Deficiency Diseases
mesh term: alpha-Mannosidosis