<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/NCT02993796</url>
  </required_header>
  <id_info>
    <org_study_id>RDCRN6726</org_study_id>
    <secondary_id>1R01HD104814-01A1</secondary_id>
    <nct_id>NCT02993796</nct_id>
  </id_info>
  <brief_title>Krabbe Disease Global Patient Registry</brief_title>
  <official_title>The Institute for Myelin and Glia Exploration's Clinical Database of Patients With Krabbe Disease, A World-Wide Registry</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>State University of New York at Buffalo</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Rare Diseases Clinical Research Network</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Center for Advancing Translational Sciences (NCATS)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Lysosomal Disease Network</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>State University of New York at Buffalo</source>
  <oversight_info>
    <has_dmc>Yes</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>
      The purpose of this study is to develop a clinical database of individuals diagnosed with&#xD;
      Krabbe disease in order to determine which symptoms herald the onset of clinical disease in&#xD;
      the various phenotypes of Krabbe disease; to determine whether level of GALC enzyme activity,&#xD;
      or a specific genetic mutation predict the clinical course; and to determine which&#xD;
      neurodiagnostic tests predict onset and/or severity of the disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purported incidence of Krabbe disease is 1/250,000 live births. It is believed that&#xD;
      80-90% of affected children will have the early-infantile form of the disease. Other forms of&#xD;
      the disease, however, occur throughout life. Unfortunately neither enzyme activity levels nor&#xD;
      specific genetic mutation reliably predict phenotype. Since the only treatment for Krabbe&#xD;
      disease is bone marrow transplantation, it is crucial to be able to identify prognostic&#xD;
      factors, which will accurately predict the disease course. At this time the medical&#xD;
      literature is limited regarding the clinical signs and symptoms of the later-onset forms of&#xD;
      Krabbe disease, as well as their age of onset, and survival of these individuals.&#xD;
&#xD;
      Early-infantile Krabbe disease has a uniformly fatal outcome if untreated, and later-onset&#xD;
      forms remain at-risk for developing symptoms. The only available treatment, pooled cord-blood&#xD;
      transplantation, has a 10-20% mortality rate.&#xD;
&#xD;
      The vast majority of children who screen positively for Krabbe disease during newborn&#xD;
      screening have an uncertain prognosis. No single diagnostic test available currently can&#xD;
      accurately predict the onset of symptoms. Consequently, improved phenotypic understanding&#xD;
      will enhance the diagnostic paradigm for Krabbe disease, and will facilitate more timely&#xD;
      diagnosis and treatment.&#xD;
&#xD;
      The information collected in the registry will be used to improve accuracy of diagnosis, and&#xD;
      to prevent children who are not destined to develop Krabbe from being subjected unnecessarily&#xD;
      to treatment.&#xD;
&#xD;
      The hypotheses to be tested include:&#xD;
&#xD;
        -  a detailed database will broaden phenotypic understanding of Krabbe disease;&#xD;
&#xD;
        -  new therapies will result from better phenotypic understanding of this disorder.&#xD;
&#xD;
      A questionnaire will be collected at time of enrollment with information pertaining to an&#xD;
      individual affected by Krabbe disease. Clinical information to be collected will include: age&#xD;
      at onset of symptoms; type of symptoms; age at diagnosis; level of GALC enzyme activity;&#xD;
      identification of the specific genetic mutation; results of any available brain MRI imaging&#xD;
      evaluations; results of any available spinal fluid protein analyses; results of any available&#xD;
      brainstem auditory evoked response evaluations; results of any available visual evoked&#xD;
      response evaluations; and results of any available nerve-conduction-velocity studies. If&#xD;
      possible, CD-ROMs containing the imaging data and physician reports of brain MRI imaging&#xD;
      evaluations will be obtained. Potential prognostic indicators based on molecular genetic&#xD;
      results, GALC enzyme level, detected potential biomarkers, and neurodiagnostic testing will&#xD;
      be analyzed. Information on the status of participant's general health, disease progression,&#xD;
      impact of the disease, neurologic symptoms, and developmental milestones will be collected&#xD;
      through follow-up phone calls with parents or caregivers.&#xD;
&#xD;
      After de-identification, the data will be entered into the Krabbe clinical database at the&#xD;
      University at Buffalo's Center of Excellence in Bioinformatics, and/or the Population Health&#xD;
      Observatory on the South Campus, and/or the Longitudinal Pediatric Data Resource, a tool&#xD;
      provided by the Newborn Screening Translational Research Network.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 2014</start_date>
  <completion_date type="Anticipated">September 2024</completion_date>
  <primary_completion_date type="Anticipated">September 2024</primary_completion_date>
  <study_type>Observational [Patient Registry]</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>
  <target_duration>5 Years</target_duration>
  <primary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>up to 5 years</time_frame>
    <description>The longevity of participants will be recorded using their date of death, or conclusion of this study, whichever occurs first.</description>
  </primary_outcome>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Krabbe Disease</condition>
  <eligibility>
    <study_pop>
      <textblock>
        This study seeks enrollment by anyone of any age or gender who has been diagnosed with&#xD;
        Krabbe disease, and also:&#xD;
&#xD;
          -  Anyone at-risk for Krabbe disease&#xD;
&#xD;
          -  Family members of someone diagnosed with, or at-risk for, Krabbe disease. This may&#xD;
             consist of adults unable to consent; individuals who are not yet adults; and pregnant&#xD;
             women.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Anyone diagnosed with Krabbe disease&#xD;
&#xD;
          -  Anyone at-risk for Krabbe disease&#xD;
&#xD;
          -  Family members of someone diagnosed with, or at-risk for, Krabbe disease.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Anyone who is not diagnosed with, or at-risk for, Krabbe disease&#xD;
&#xD;
          -  Anyone who is not a family member of someone diagnosed with, or at-risk for, Krabbe&#xD;
             disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Thomas J. Langan, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Clinical Director, Clinical Research, Institute for Myelin and Glial Exploration</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Thomas J. Langan, MD</last_name>
    <phone>716-888-4732</phone>
    <email>tjlangan@buffalo.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Amy Barczykowski</last_name>
    <phone>716-829-6101</phone>
    <email>alp38@buffalo.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>State University of New York at Buffalo</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14203</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Thomas J. Langan, MD</last_name>
      <phone>716-888-4732</phone>
      <email>tjlangan@buffalo.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://hjkri.buffalo.edu/</url>
    <description>Hunter James Kelly Research Institute, University at Buffalo - home page</description>
  </link>
  <link>
    <url>http://huntershope.org/</url>
    <description>Hunter's Hope Foundation, one of the funders of this research study - their home page</description>
  </link>
  <link>
    <url>https://www.nbstrn.org/</url>
    <description>Newborn Screening Translational Research Network - their home page</description>
  </link>
  <link>
    <url>http://www.LysosomalDiseaseNetwork.org</url>
    <description>Lysosomal Disease Network, one of the funders of this research study - their home page</description>
  </link>
  <link>
    <url>https://www.nichd.nih.gov/Pages/index.aspx</url>
    <description>Eunice Kennedy Shriver National Institute of Child Health and Human Development</description>
  </link>
  <link>
    <url>https://www.rarediseasesnetwork.org/</url>
    <description>Rare Diseases Clinical Research Network, the funder of the Lysosomal Disease Network</description>
  </link>
  <reference>
    <citation>Carter RL, Wrabetz L, Jalal K, Orsini JJ, Barczykowski AL, Matern D, Langan TJ. Can psychosine and galactocerebrosidase activity predict early-infantile Krabbe's disease presymptomatically? J Neurosci Res. 2016 Nov;94(11):1084-93. doi: 10.1002/jnr.23793.</citation>
    <PMID>27638594</PMID>
  </reference>
  <reference>
    <citation>Langan TJ, Barcykowski AL, Dare J, Pannullo EC, Muscarella L, Carter RL. Evidence for improved survival in postsymptomatic stem cell-transplanted patients with Krabbe's disease. J Neurosci Res. 2016 Nov;94(11):1189-94. doi: 10.1002/jnr.23787.</citation>
    <PMID>27638603</PMID>
  </reference>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>December 6, 2016</study_first_submitted>
  <study_first_submitted_qc>December 13, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 15, 2016</study_first_posted>
  <last_update_submitted>July 25, 2023</last_update_submitted>
  <last_update_submitted_qc>July 25, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 27, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>State University of New York at Buffalo</investigator_affiliation>
    <investigator_full_name>Thomas J. Langan</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Krabbe disease</keyword>
  <keyword>globoid cell leukodystrophy</keyword>
  <keyword>galactosylceramide lipidosis</keyword>
  <keyword>sphingolipidosis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukodystrophy, Globoid Cell</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>De-identified individual data is input to the NIH-funded Rare Diseases Clinical Research Network's Data Management &amp; Coordinating Center (&quot;DMCC&quot;). Eventually this data will become part of the database of Genotypes and Phenotypes (&quot;dbGaP&quot;), which is part of the National Center for Biotechnology Information, U.S. National Library of Medicine.</ipd_description>
  </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/NCT02993796
org study id: RDCRN6726
secondary id: 1R01HD104814-01A1
nct id: NCT02993796
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to develop a clinical database of individuals diagnosed with
      Krabbe disease in order to determine which symptoms herald the onset of clinical disease in
      the various phenotypes of Krabbe disease; to determine whether level of GALC enzyme activity,
      or a specific genetic mutation predict the clinical course; and to determine which
      neurodiagnostic tests predict onset and/or severity of the disease.
The purported incidence of Krabbe disease is 1/250,000 live births. It is believed that
      80-90% of affected children will have the early-infantile form of the disease. Other forms of
      the disease, however, occur throughout life. Unfortunately neither enzyme activity levels nor
      specific genetic mutation reliably predict phenotype. Since the only treatment for Krabbe
      disease is bone marrow transplantation, it is crucial to be able to identify prognostic
      factors, which will accurately predict the disease course. At this time the medical
      literature is limited regarding the clinical signs and symptoms of the later-onset forms of
      Krabbe disease, as well as their age of onset, and survival of these individuals.

      Early-infantile Krabbe disease has a uniformly fatal outcome if untreated, and later-onset
      forms remain at-risk for developing symptoms. The only available treatment, pooled cord-blood
      transplantation, has a 10-20% mortality rate.

      The vast majority of children who screen positively for Krabbe disease during newborn
      screening have an uncertain prognosis. No single diagnostic test available currently can
      accurately predict the onset of symptoms. Consequently, improved phenotypic understanding
      will enhance the diagnostic paradigm for Krabbe disease, and will facilitate more timely
      diagnosis and treatment.

      The information collected in the registry will be used to improve accuracy of diagnosis, and
      to prevent children who are not destined to develop Krabbe from being subjected unnecessarily
      to treatment.

      The hypotheses to be tested include:

        -  a detailed database will broaden phenotypic understanding of Krabbe disease;

        -  new therapies will result from better phenotypic understanding of this disorder.

      A questionnaire will be collected at time of enrollment with information pertaining to an
      individual affected by Krabbe disease. Clinical information to be collected will include: age
      at onset of symptoms; type of symptoms; age at diagnosis; level of GALC enzyme activity;
      identification of the specific genetic mutation; results of any available brain MRI imaging
      evaluations; results of any available spinal fluid protein analyses; results of any available
      brainstem auditory evoked response evaluations; results of any available visual evoked
      response evaluations; and results of any available nerve-conduction-velocity studies. If
      possible, CD-ROMs containing the imaging data and physician reports of brain MRI imaging
      evaluations will be obtained. Potential prognostic indicators based on molecular genetic
      results, GALC enzyme level, detected potential biomarkers, and neurodiagnostic testing will
      be analyzed. Information on the status of participant's general health, disease progression,
      impact of the disease, neurologic symptoms, and developmental milestones will be collected
      through follow-up phone calls with parents or caregivers.

      After de-identification, the data will be entered into the Krabbe clinical database at the
      University at Buffalo's Center of Excellence in Bioinformatics, and/or the Population Health
      Observatory on the South Campus, and/or the Longitudinal Pediatric Data Resource, a tool
      provided by the Newborn Screening Translational Research Network.
observational model: Cohort
time perspective: Prospective
measure: Overall Survival
time frame: up to 5 years
description: The longevity of participants will be recorded using their date of death, or conclusion of this study, whichever occurs first.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Thomas J. Langan, MD
role: Principal Investigator
affiliation: Clinical Director, Clinical Research, Institute for Myelin and Glial Exploration
last name: Thomas J. Langan, MD
phone: 716-888-4732
email: tjlangan@buffalo.edu
last name: Amy Barczykowski
phone: 716-829-6101
email: alp38@buffalo.edu
facility: 
status: Recruiting
contact: 
country: United States
url: http://hjkri.buffalo.edu/
description: Hunter James Kelly Research Institute, University at Buffalo - home page
url: http://huntershope.org/
description: Hunter's Hope Foundation, one of the funders of this research study - their home page
url: https://www.nbstrn.org/
description: Newborn Screening Translational Research Network - their home page
url: http://www.LysosomalDiseaseNetwork.org
description: Lysosomal Disease Network, one of the funders of this research study - their home page
url: https://www.nichd.nih.gov/Pages/index.aspx
description: Eunice Kennedy Shriver National Institute of Child Health and Human Development
url: https://www.rarediseasesnetwork.org/
description: Rare Diseases Clinical Research Network, the funder of the Lysosomal Disease Network
citation: Carter RL, Wrabetz L, Jalal K, Orsini JJ, Barczykowski AL, Matern D, Langan TJ. Can psychosine and galactocerebrosidase activity predict early-infantile Krabbe's disease presymptomatically? J Neurosci Res. 2016 Nov;94(11):1084-93. doi: 10.1002/jnr.23793.
PMID: 27638594
citation: Langan TJ, Barcykowski AL, Dare J, Pannullo EC, Muscarella L, Carter RL. Evidence for improved survival in postsymptomatic stem cell-transplanted patients with Krabbe's disease. J Neurosci Res. 2016 Nov;94(11):1189-94. doi: 10.1002/jnr.23787.
PMID: 27638603
responsible party type: Principal Investigator
investigator affiliation: State University of New York at Buffalo
investigator full name: Thomas J. Langan
investigator title: Principal Investigator
mesh term: Leukodystrophy, Globoid Cell
sharing ipd: Yes
ipd description: De-identified individual data is input to the NIH-funded Rare Diseases Clinical Research Network's Data Management & Coordinating Center ("DMCC"). Eventually this data will become part of the database of Genotypes and Phenotypes ("dbGaP"), which is part of the National Center for Biotechnology Information, U.S. National Library of Medicine.