<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/NCT01668186</url>
  </required_header>
  <id_info>
    <org_study_id>11-090-PED</org_study_id>
    <nct_id>NCT01668186</nct_id>
  </id_info>
  <brief_title>Longitudinal Natural History Study of Patients With Peroxisome Biogenesis Disorders (PBD)</brief_title>
  <official_title>Longitudinal Natural History Study of Patients With Peroxisome Biogenesis Disorders (PBD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>McGill University Health Centre/Research Institute of the McGill University Health Centre</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>McGill University Health Centre/Research Institute of the McGill University Health Centre</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The Peroxisome Biogenesis Disorders (PBD) are a group of inherited disorders due to defects&#xD;
      in peroxisome assembly causing complex developmental and metabolic sequelae. In spite of&#xD;
      advancements in peroxisome biology, the pathophysiology remains unknown, the spectrum of&#xD;
      phenotypes poorly characterized and the natural history not yet systematically reported. Our&#xD;
      aims are to further define this population clinically, biochemically and genetically. The&#xD;
      investigators will prospectively follow patients from Canada, the US and internationally, and&#xD;
      collect data from medical evaluations, blood, urine and imaging studies that would be&#xD;
      performed on a clinical care basis. For patients who are unable to attend our clinic, we will&#xD;
      collect all medical records and images since birth as well as subsequent records/images for&#xD;
      the next 5 years or until the end of the study. Clinical data from medical records will be&#xD;
      banked in our Peroxisomal Disorder Research Databank and Biobank. The investigators will use&#xD;
      this information to identify standards of care and improve management.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Participants have the option to be seen in consultation at the McGill University Health&#xD;
      Centre in Montreal, Canada, on a yearly basis. This includes a consultation in Genetics,&#xD;
      Nutrition, Neurology, and Ophthalmology (OCT and FAF exams). All medical records and images&#xD;
      will be collected, retrospectively and prospectively, until the end of the study, and entered&#xD;
      anonymously in a database. Biospecimens will be collected to identify new biomarkers.&#xD;
      Candidate drugs will be evaluated for recovery of peroxisome functions in cultured&#xD;
      fibroblasts.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 2012</start_date>
  <completion_date type="Anticipated">January 2025</completion_date>
  <primary_completion_date type="Anticipated">January 2025</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>Other</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Documentation of the clinical findings</measure>
    <time_frame>Yearly up to 10 years</time_frame>
    <description>Clinical findings include but are not limited to: life span, growth parameters, development, vision, hearing, neurological examinations, renal problems, adrenal function, skeletal problems, and any other system involvement.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Peroxisome function testing</measure>
    <time_frame>Yearly up to 10 years</time_frame>
    <description>To include very long chain saturated, branched and polyunsaturated fatty acids, bile acids, plasmalogens, pipecolic acid, adrenal functions, liver functions, and urine oxalate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Development of leukodystrophy</measure>
    <time_frame>Yearly up to 10 years</time_frame>
    <description>Identification of patterns and course by MRI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Scoring of fundus photography (OCT and FAF)</measure>
    <time_frame>Yearly up to 10 years</time_frame>
    <description>Identification of patterns and course</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Genotype-phenotype correlation</measure>
    <time_frame>Yearly up to 10 years</time_frame>
    <description>Correlation of mutation type to peroxisome biochemistry, number and type of disease complications.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of various disease complications and identification of risk factors in the PBD population</measure>
    <time_frame>Yearly up to 10 years</time_frame>
    <description>Neurological, vision, hearing, liver dysfunction, adrenal insufficiency, osteopenia, renal stones</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Development of care management guideline resource for adolescents and adults with PBD-ZSD</measure>
    <time_frame>Yearly up to 10 years</time_frame>
    <description>Medical issues (Neurological, vision, hearing, liver dysfunction, adrenal insufficiency, osteopenia, renal stones), main challenges, and the pediatric-to-adult transition experience will be included in PBD-ZSD adult-specific management guidelines</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">230</enrollment>
  <condition>Peroxisome Biogenesis Disorder</condition>
  <condition>Zellweger Spectrum Disorder</condition>
  <condition>RCDP - Rhizomelic Chondrodysplasia Punctata</condition>
  <condition>D-Bifunctional Protein Deficiency</condition>
  <condition>Alpha-Methylacyl-CoA Racemase Deficiency</condition>
  <condition>Peroxisomal Acyl-CoA Oxidase Deficiency</condition>
  <condition>Peroxisomal Acyl-CoA Oxidase 2 Deficiency</condition>
  <condition>ATP Binding Cassette Subfamily D Member 3 Gene Mutation</condition>
  <condition>ACBD5 (AcylCoA Binding Domain 5) Deficiency</condition>
  <condition>Adult Refsum Disease</condition>
  <condition>Sterol Carrier Protein 2 Deficiency</condition>
  <arm_group>
    <arm_group_label>Patients diagnosed with a peroxisomal disorder</arm_group_label>
    <description>Collection of medical records and images (ultrasounds, X-rays, MRIs, CT scans, ophthalmic images), Next-generation panel, Drug screening, and Consultation</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      blood, dried blood spots, urine, and specimens obtained for other e.g. cultured fibroblasts,&#xD;
      liver biopsies&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Any patient with a PBD diagnosis- or related single enzyme/protein defect&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of PBD or&#xD;
&#xD;
          -  Single peroxisome enzyme/protein defect with phenotype similar to PBD&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Not a PBD&#xD;
&#xD;
          -  Not a single peroxisome enzyme/protein defect with phenotype similar to PBD&#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>Nancy E Braverman, MD, MS</last_name>
    <role>Principal Investigator</role>
    <affiliation>McGill University Health Center, Montreal Childrens Hopital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Nancy E Braverman, MD, MS</last_name>
    <phone>(1) 514-934-1934</phone>
    <phone_ext>23404</phone_ext>
    <email>nancy.braverman@mcgill.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Hermine Djimoudi, MSc</last_name>
    <phone>(1) 514-934-1934</phone>
    <phone_ext>23403</phone_ext>
    <email>pbd.genetics@mcgill.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Research Institute of the McGill University Health Center</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H4A 3J1</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Nancy E Braverman, MD, MS</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <reference>
    <citation>Steinberg SJ, Raymond GV, Braverman NE, Moser AB. Zellweger Spectrum Disorder. 2003 Dec 12 [updated 2020 Oct 29]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from http://www.ncbi.nlm.nih.gov/books/NBK1448/</citation>
    <PMID>20301621</PMID>
  </reference>
  <reference>
    <citation>Braverman NE, Raymond GV, Rizzo WB, Moser AB, Wilkinson ME, Stone EM, Steinberg SJ, Wangler MF, Rush ET, Hacia JG, Bose M. Peroxisome biogenesis disorders in the Zellweger spectrum: An overview of current diagnosis, clinical manifestations, and treatment guidelines. Mol Genet Metab. 2016 Mar;117(3):313-21. doi: 10.1016/j.ymgme.2015.12.009. Epub 2015 Dec 23.</citation>
    <PMID>26750748</PMID>
  </reference>
  <reference>
    <citation>Braverman NE, Steinberg SJ, Fallatah W, Duker A, Bober MB. Rhizomelic Chondrodysplasia Punctata Type 1. 2001 Nov 16 [updated 2020 Jan 30]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from http://www.ncbi.nlm.nih.gov/books/NBK1270/</citation>
    <PMID>20301447</PMID>
  </reference>
  <reference>
    <citation>Rush ET, Goodwin JL, Braverman NE, Rizzo WB. Low bone mineral density is a common feature of Zellweger spectrum disorders. Mol Genet Metab. 2016 Jan;117(1):33-7. doi: 10.1016/j.ymgme.2015.11.009. Epub 2015 Nov 24.</citation>
    <PMID>26643206</PMID>
  </reference>
  <reference>
    <citation>Wangler MF, Hubert L, Donti TR, Ventura MJ, Miller MJ, Braverman N, Gawron K, Bose M, Moser AB, Jones RO, Rizzo WB, Sutton VR, Sun Q, Kennedy AD, Elsea SH. A metabolomic map of Zellweger spectrum disorders reveals novel disease biomarkers. Genet Med. 2018 Oct;20(10):1274-1283. doi: 10.1038/gim.2017.262. Epub 2018 Feb 8.</citation>
    <PMID>29419819</PMID>
  </reference>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>August 10, 2012</study_first_submitted>
  <study_first_submitted_qc>August 14, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 17, 2012</study_first_posted>
  <last_update_submitted>July 4, 2022</last_update_submitted>
  <last_update_submitted_qc>July 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 6, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>McGill University Health Centre/Research Institute of the McGill University Health Centre</investigator_affiliation>
    <investigator_full_name>Nancy Braverman</investigator_full_name>
    <investigator_title>MD, M.Sc. Professor, Depts. of Human Genetics and Pediatrics</investigator_title>
  </responsible_party>
  <keyword>Peroxisome biogenesis disorders</keyword>
  <keyword>PBD</keyword>
  <keyword>Zellweger spectrum disorder</keyword>
  <keyword>Rhizomelic chondrodysplasia punctata</keyword>
  <keyword>DBP</keyword>
  <keyword>ACOX1</keyword>
  <keyword>AMACR</keyword>
  <keyword>ARD</keyword>
  <keyword>ACBD5</keyword>
  <keyword>ZSD</keyword>
  <keyword>RCDP</keyword>
  <keyword>ACOX2</keyword>
  <keyword>ABCD3</keyword>
  <keyword>Adult Refsum</keyword>
  <keyword>PHYH</keyword>
  <keyword>SCPx</keyword>
  <keyword>RCDP1</keyword>
  <keyword>RCDP2</keyword>
  <keyword>RCDP3</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Chondrodysplasia Punctata, Rhizomelic</mesh_term>
    <mesh_term>Chondrodysplasia Punctata</mesh_term>
    <mesh_term>Zellweger Syndrome</mesh_term>
    <mesh_term>Refsum Disease</mesh_term>
    <mesh_term>Peroxisomal Disorders</mesh_term>
    <mesh_term>Protein Deficiency</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/NCT01668186
org study id: 11-090-PED
nct id: NCT01668186
lead sponsor: 
has dmc: No
The Peroxisome Biogenesis Disorders (PBD) are a group of inherited disorders due to defects
      in peroxisome assembly causing complex developmental and metabolic sequelae. In spite of
      advancements in peroxisome biology, the pathophysiology remains unknown, the spectrum of
      phenotypes poorly characterized and the natural history not yet systematically reported. Our
      aims are to further define this population clinically, biochemically and genetically. The
      investigators will prospectively follow patients from Canada, the US and internationally, and
      collect data from medical evaluations, blood, urine and imaging studies that would be
      performed on a clinical care basis. For patients who are unable to attend our clinic, we will
      collect all medical records and images since birth as well as subsequent records/images for
      the next 5 years or until the end of the study. Clinical data from medical records will be
      banked in our Peroxisomal Disorder Research Databank and Biobank. The investigators will use
      this information to identify standards of care and improve management.
Participants have the option to be seen in consultation at the McGill University Health
      Centre in Montreal, Canada, on a yearly basis. This includes a consultation in Genetics,
      Nutrition, Neurology, and Ophthalmology (OCT and FAF exams). All medical records and images
      will be collected, retrospectively and prospectively, until the end of the study, and entered
      anonymously in a database. Biospecimens will be collected to identify new biomarkers.
      Candidate drugs will be evaluated for recovery of peroxisome functions in cultured
      fibroblasts.
observational model: Cohort
time perspective: Other
measure: Documentation of the clinical findings
time frame: Yearly up to 10 years
description: Clinical findings include but are not limited to: life span, growth parameters, development, vision, hearing, neurological examinations, renal problems, adrenal function, skeletal problems, and any other system involvement.
measure: Peroxisome function testing
time frame: Yearly up to 10 years
description: To include very long chain saturated, branched and polyunsaturated fatty acids, bile acids, plasmalogens, pipecolic acid, adrenal functions, liver functions, and urine oxalate.
measure: Development of leukodystrophy
time frame: Yearly up to 10 years
description: Identification of patterns and course by MRI
measure: Scoring of fundus photography (OCT and FAF)
time frame: Yearly up to 10 years
description: Identification of patterns and course
measure: Genotype-phenotype correlation
time frame: Yearly up to 10 years
description: Correlation of mutation type to peroxisome biochemistry, number and type of disease complications.
measure: Frequency of various disease complications and identification of risk factors in the PBD population
time frame: Yearly up to 10 years
description: Neurological, vision, hearing, liver dysfunction, adrenal insufficiency, osteopenia, renal stones
measure: Development of care management guideline resource for adolescents and adults with PBD-ZSD
time frame: Yearly up to 10 years
description: Medical issues (Neurological, vision, hearing, liver dysfunction, adrenal insufficiency, osteopenia, renal stones), main challenges, and the pediatric-to-adult transition experience will be included in PBD-ZSD adult-specific management guidelines
arm group label: Patients diagnosed with a peroxisomal disorder
description: Collection of medical records and images (ultrasounds, X-rays, MRIs, CT scans, ophthalmic images), Next-generation panel, Drug screening, and Consultation
blood, dried blood spots, urine, and specimens obtained for other e.g. cultured fibroblasts,
      liver biopsies
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Nancy E Braverman, MD, MS
role: Principal Investigator
affiliation: McGill University Health Center, Montreal Childrens Hopital
last name: Nancy E Braverman, MD, MS
phone: (1) 514-934-1934
phone ext: 23404
email: nancy.braverman@mcgill.ca
last name: Hermine Djimoudi, MSc
phone: (1) 514-934-1934
phone ext: 23403
email: pbd.genetics@mcgill.ca
facility: 
status: Recruiting
investigator: 
country: Canada
citation: Steinberg SJ, Raymond GV, Braverman NE, Moser AB. Zellweger Spectrum Disorder. 2003 Dec 12 [updated 2020 Oct 29]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from http://www.ncbi.nlm.nih.gov/books/NBK1448/
PMID: 20301621
citation: Braverman NE, Raymond GV, Rizzo WB, Moser AB, Wilkinson ME, Stone EM, Steinberg SJ, Wangler MF, Rush ET, Hacia JG, Bose M. Peroxisome biogenesis disorders in the Zellweger spectrum: An overview of current diagnosis, clinical manifestations, and treatment guidelines. Mol Genet Metab. 2016 Mar;117(3):313-21. doi: 10.1016/j.ymgme.2015.12.009. Epub 2015 Dec 23.
PMID: 26750748
citation: Braverman NE, Steinberg SJ, Fallatah W, Duker A, Bober MB. Rhizomelic Chondrodysplasia Punctata Type 1. 2001 Nov 16 [updated 2020 Jan 30]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from http://www.ncbi.nlm.nih.gov/books/NBK1270/
PMID: 20301447
citation: Rush ET, Goodwin JL, Braverman NE, Rizzo WB. Low bone mineral density is a common feature of Zellweger spectrum disorders. Mol Genet Metab. 2016 Jan;117(1):33-7. doi: 10.1016/j.ymgme.2015.11.009. Epub 2015 Nov 24.
PMID: 26643206
citation: Wangler MF, Hubert L, Donti TR, Ventura MJ, Miller MJ, Braverman N, Gawron K, Bose M, Moser AB, Jones RO, Rizzo WB, Sutton VR, Sun Q, Kennedy AD, Elsea SH. A metabolomic map of Zellweger spectrum disorders reveals novel disease biomarkers. Genet Med. 2018 Oct;20(10):1274-1283. doi: 10.1038/gim.2017.262. Epub 2018 Feb 8.
PMID: 29419819
responsible party type: Principal Investigator
investigator affiliation: McGill University Health Centre/Research Institute of the McGill University Health Centre
investigator full name: Nancy Braverman
investigator title: MD, M.Sc. Professor, Depts. of Human Genetics and Pediatrics
mesh term: Chondrodysplasia Punctata, Rhizomelic
mesh term: Chondrodysplasia Punctata
mesh term: Zellweger Syndrome
mesh term: Refsum Disease
mesh term: Peroxisomal Disorders
mesh term: Protein Deficiency