<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/NCT03812042</url>
  </required_header>
  <id_info>
    <org_study_id>16-LDRTC-04</org_study_id>
    <nct_id>NCT03812042</nct_id>
  </id_info>
  <brief_title>Screening of Lysosomal Storage Disorders Diseases in Minority Groups</brief_title>
  <official_title>Enzymatic and Genotypic Screening of Lysosomal Storage Diseases in Minority Groups</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Lysosomal and Rare Disorders Research and Treatment Center, Inc.</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Lysosomal and Rare Disorders Research and Treatment Center, Inc.</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>
      Aim is to undertake a screening study that identifies undiagnosed patients with LSDs and&#xD;
      determine the prevalence of these diseases with special focus on underrepresented minority&#xD;
      groups.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Lysosomes are small, cytoplasmic organelles that contain several acid hydrolase enzymes.&#xD;
      These enzymes break down foreign materials and cellular debris allowing the lysosomes to act&#xD;
      as recycling centers for the cells. Following DNA transcription, lysosomal enzymes are&#xD;
      produced in the endoplasmic reticulum and targeted to lysosomes by specific recognition&#xD;
      markers. If one of the enzymes is absent or if its function is diminished due to either an&#xD;
      altered amino acid sequence of the protein or defective intracellular trafficking, the&#xD;
      macromolecules metabolized by the specific enzyme will gradually accumulate in the lysosomes.&#xD;
      Abnormal substrate storage leads to cellular dysfunction followed by cell death ultimately&#xD;
      manifesting as tissue damage and organ failure.&#xD;
&#xD;
      More than 50 metabolic disorders resulting from defective lysosomal enzyme function have been&#xD;
      described and are classified as lysosomal storage disorders (LSDs). Although individually&#xD;
      uncommon (less than 1 in 100,000), the combined incidence of this group of genetic disorders&#xD;
      is about 1 in 5,000 to 1 in 10,000. The prevalence might be even higher than predicted due to&#xD;
      undiagnosed instances or misdiagnosis of milder cases.&#xD;
&#xD;
      Most of LSDs are inherited in an autosomal recessive manner except two disorders: Fabry&#xD;
      disease and Hunter syndrome, which are X chromosome linked. Two healthy carriers of the same&#xD;
      autosomal recessive disease may have an affected child. Usually the carriers are unaware of&#xD;
      their carrier status prior to screening or until they have a sick child. These disorders are&#xD;
      more common in communities with high consanguinity and where cousin marriages are allowed. In&#xD;
      the case of X-linked diseases, the mutant gene is passed down from one generation to the next&#xD;
      one in a specific way. If a male has an abnormal copy of the specific gene, he will show the&#xD;
      typical presentation of the disease. If a woman has an abnormal copy of the specific gene,&#xD;
      she may develop some milder symptoms of the disease due to random X- inactivation.&#xD;
&#xD;
      Screening for LSDs is performed by measuring enzymatic activity in peripheral blood. The most&#xD;
      cost effective and convenient way is to use dried filter paper blood spots. A positive&#xD;
      screening result has to be followed by a confirmatory enzymatic testing using white blood&#xD;
      cells, plasma or cultured skin fibroblasts and/or DNA mutation analysis. The importance of&#xD;
      screening for LSDs has been recognized by several state governments as these tests are being&#xD;
      included in many newborn screening programs. Although newborn screening helps to identify&#xD;
      patients early on, there is still an unmet need for population screening and for identifying&#xD;
      patients with reversible tissue damage. LSDs cause serious and progressive problems with&#xD;
      multiple body systems. Therapy is available and is promising in most cases. Importantly,&#xD;
      patients with LSDs require thorough management plans for their complex health issues.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">March 17, 2016</start_date>
  <completion_date type="Anticipated">December 2019</completion_date>
  <primary_completion_date type="Anticipated">December 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Ecologic or Community</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Enzyme activity analysis to identify subjects with Lysosomal storage disorders</measure>
    <time_frame>5 years</time_frame>
    <description>To identify patients with LSDs using enzymatic activity specific to individual lysosomal storage disorders using left-over blood of blood samples collected as part of standard clinical care.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Genotypic analysis of subjects with abnormal enzyme activity</measure>
    <time_frame>5 years</time_frame>
    <description>Samples from subjects with abnormally low enzyme activity will be used for targeted sequencing analysis to diagnose any pathologic mutations.</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">100000</enrollment>
  <condition>Lysosomal Storage Diseases</condition>
  <arm_group>
    <arm_group_label>Screen population</arm_group_label>
    <description>The study population will comprise of patients of healthcare institutions in the Washington, D.C. metro area including but not limited to hospitals, clinics, and doctor's offices.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Enzyme assay and molecular sequencing</intervention_name>
    <description>Enzyme assay and molecular sequencing on relevant samples conducted from left over blood samples</description>
    <arm_group_label>Screen population</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        The study population will comprise of patients of healthcare institutions in the&#xD;
        Washington, D.C. and Richmond, Virginia areas including but not limited to hospitals,&#xD;
        clinics, and doctor's offices.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  To be enrolled in this study the subject must meet the following (inclusion) criteria:&#xD;
&#xD;
               -  Subject is greater than or equal to 1 day of age and less than or equal to 100&#xD;
                  years of age&#xD;
&#xD;
               -  Subject is managed by a physician in the Washington, D.C and Richmond, VA metro&#xD;
                  area&#xD;
&#xD;
               -  Subject is getting blood work as part of standard clinical care and there is at&#xD;
                  least 60 uL blood remained in a tube after all clinical tests were run&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  subjects must not meet any of the following (exclusion) criteria:&#xD;
&#xD;
               -  Absolute contraindication for blood drawing&#xD;
&#xD;
               -  Subject cannot be traced back by the referring physician upon a positive&#xD;
                  screening result&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Renuka Limgala, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>LDRTC</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Margarita M Ivanova, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>LDRTC</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ozlem Goker-Alpan, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>LDRTC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>LDRTC</name>
      <address>
        <city>Fairfax</city>
        <state>Virginia</state>
        <zip>22030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.ldrtc.org</url>
    <description>Institute website for more details</description>
  </link>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 18, 2019</study_first_submitted>
  <study_first_submitted_qc>January 18, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 22, 2019</study_first_posted>
  <last_update_submitted>January 18, 2019</last_update_submitted>
  <last_update_submitted_qc>January 18, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 22, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Gaucher disease</keyword>
  <keyword>Fabry disease</keyword>
  <keyword>Pompe disease</keyword>
  <keyword>Gangliosidoses</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lysosomal Storage Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03812042
org study id: 16-LDRTC-04
nct id: NCT03812042
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Aim is to undertake a screening study that identifies undiagnosed patients with LSDs and
      determine the prevalence of these diseases with special focus on underrepresented minority
      groups.
Lysosomes are small, cytoplasmic organelles that contain several acid hydrolase enzymes.
      These enzymes break down foreign materials and cellular debris allowing the lysosomes to act
      as recycling centers for the cells. Following DNA transcription, lysosomal enzymes are
      produced in the endoplasmic reticulum and targeted to lysosomes by specific recognition
      markers. If one of the enzymes is absent or if its function is diminished due to either an
      altered amino acid sequence of the protein or defective intracellular trafficking, the
      macromolecules metabolized by the specific enzyme will gradually accumulate in the lysosomes.
      Abnormal substrate storage leads to cellular dysfunction followed by cell death ultimately
      manifesting as tissue damage and organ failure.

      More than 50 metabolic disorders resulting from defective lysosomal enzyme function have been
      described and are classified as lysosomal storage disorders (LSDs). Although individually
      uncommon (less than 1 in 100,000), the combined incidence of this group of genetic disorders
      is about 1 in 5,000 to 1 in 10,000. The prevalence might be even higher than predicted due to
      undiagnosed instances or misdiagnosis of milder cases.

      Most of LSDs are inherited in an autosomal recessive manner except two disorders: Fabry
      disease and Hunter syndrome, which are X chromosome linked. Two healthy carriers of the same
      autosomal recessive disease may have an affected child. Usually the carriers are unaware of
      their carrier status prior to screening or until they have a sick child. These disorders are
      more common in communities with high consanguinity and where cousin marriages are allowed. In
      the case of X-linked diseases, the mutant gene is passed down from one generation to the next
      one in a specific way. If a male has an abnormal copy of the specific gene, he will show the
      typical presentation of the disease. If a woman has an abnormal copy of the specific gene,
      she may develop some milder symptoms of the disease due to random X- inactivation.

      Screening for LSDs is performed by measuring enzymatic activity in peripheral blood. The most
      cost effective and convenient way is to use dried filter paper blood spots. A positive
      screening result has to be followed by a confirmatory enzymatic testing using white blood
      cells, plasma or cultured skin fibroblasts and/or DNA mutation analysis. The importance of
      screening for LSDs has been recognized by several state governments as these tests are being
      included in many newborn screening programs. Although newborn screening helps to identify
      patients early on, there is still an unmet need for population screening and for identifying
      patients with reversible tissue damage. LSDs cause serious and progressive problems with
      multiple body systems. Therapy is available and is promising in most cases. Importantly,
      patients with LSDs require thorough management plans for their complex health issues.
observational model: Ecologic or Community
time perspective: Prospective
measure: Enzyme activity analysis to identify subjects with Lysosomal storage disorders
time frame: 5 years
description: To identify patients with LSDs using enzymatic activity specific to individual lysosomal storage disorders using left-over blood of blood samples collected as part of standard clinical care.
measure: Genotypic analysis of subjects with abnormal enzyme activity
time frame: 5 years
description: Samples from subjects with abnormally low enzyme activity will be used for targeted sequencing analysis to diagnose any pathologic mutations.
arm group label: Screen population
description: The study population will comprise of patients of healthcare institutions in the Washington, D.C. metro area including but not limited to hospitals, clinics, and doctor's offices.
intervention type: Diagnostic Test
intervention name: Enzyme assay and molecular sequencing
description: Enzyme assay and molecular sequencing on relevant samples conducted from left over blood samples
arm group label: Screen population
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Renuka Limgala, PhD
role: Principal Investigator
affiliation: LDRTC
last name: Margarita M Ivanova, PhD
role: Principal Investigator
affiliation: LDRTC
last name: Ozlem Goker-Alpan, MD
role: Principal Investigator
affiliation: LDRTC
facility: 
country: United States
url: http://www.ldrtc.org
description: Institute website for more details
responsible party type: Sponsor
mesh term: Lysosomal Storage Diseases
sharing ipd: Undecided