<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/NCT02263781</url>
  </required_header>
  <id_info>
    <org_study_id>S57206</org_study_id>
    <nct_id>NCT02263781</nct_id>
  </id_info>
  <brief_title>PREPL in Health and Disease</brief_title>
  <acronym>PHD</acronym>
  <official_title>PREPL in Health and Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universitaire Ziekenhuizen KU Leuven</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>KU Leuven</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Universitaire Ziekenhuizen KU Leuven</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Evaluation of PREPL activity in healthy controls and known or possible PREPL deficient&#xD;
      patients&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PREPL is defective in hypotonia cystinuria syndrome and in isolated PREPL deficiency. The&#xD;
      investigators have constructed a blood test to evaluate PREPL activity in patients with&#xD;
      possible PREPL deficiency.&#xD;
&#xD;
      The study will determine normal values for age (0-18) for PREPL activity in blood.&#xD;
&#xD;
      Also, patients with a clinical phenotype that overlaps with PREPL deficiency (including&#xD;
      patients with known primary PREPL deficiency and Prader-Willi syndrome) will be evaluated for&#xD;
      PREPL activity in blood.&#xD;
&#xD;
      A last part of the study will involve muscle biopsies during elective anesthesia/surgery for&#xD;
      other reasons. There will be 2 groups: patients without signs of PREPL deficiency undergoing&#xD;
      surgery (controls) and patients with Prader-Willi syndrome undergoing anesthesia or surgery&#xD;
      (patients). The control group will be age-matched to the hypotonia group. In the muscle&#xD;
      biopsies, PREPL activity and expression will be evaluated.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>October 2014</start_date>
  <completion_date type="Anticipated">January 2015</completion_date>
  <primary_completion_date type="Anticipated">January 2015</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>PREPL activity (ng active PREPL/g protein) normal values in blood</measure>
    <time_frame>3 months</time_frame>
    <description>normal values for PREPL activity</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PREPL activity in patients with Prader Willi syndrome compared to activity in normal controls</measure>
    <time_frame>3 months</time_frame>
    <description>Comparison of PREPL activity in blood and muscle between above mentioned groups</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PREPL activity in patients with primary PREPL deficiency compared to activity in normal controls</measure>
    <time_frame>3 months</time_frame>
    <description>Comparison of PREPL activity in blood between above mentioned groups</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PREPL activity in patients with muscle weakness/obesity/growth hormone deficiency compared to activity in normal controls</measure>
    <time_frame>3 months</time_frame>
    <description>exploratory evaluation</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Anticipated">125</enrollment>
  <condition>Hypotonia-Cystinuria Syndrome</condition>
  <condition>Muscle Hypotonia</condition>
  <condition>Healthy Volunteers</condition>
  <condition>Dwarfism, Growth Hormone Deficiency</condition>
  <condition>Obesity</condition>
  <condition>Prader-Willi Syndrome</condition>
  <arm_group>
    <arm_group_label>Control Blood</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients on routine postinfectious control, blood draw</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Primary PREPL deficiency Blood</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with primary PREPL deficiency, blood draw</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Prader Willi syndrome Blood</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with Prader-Willi syndrome, blood draw</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Primary PREPL deficiency like Blood</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with symptoms overlapping with primary PREPL deficiency (like hypotonia, growth hormone deficiency, obesity), blood draw</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control muscle</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients without hypotonia, growth hormone deficiency, obesity, undergoing elective surgery, muscle biopsy from the surgical site and blood draw</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Prader-Willli syndrome muscle</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with Prader-Willi syndrome undergoing elective anesthesia or surgery, muscle biopsy (from surgical site if applicable) and blood draw</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Blood draw</intervention_name>
    <description>Blood draw</description>
    <arm_group_label>Control Blood</arm_group_label>
    <arm_group_label>Control muscle</arm_group_label>
    <arm_group_label>Prader Willi syndrome Blood</arm_group_label>
    <arm_group_label>Prader-Willli syndrome muscle</arm_group_label>
    <arm_group_label>Primary PREPL deficiency Blood</arm_group_label>
    <arm_group_label>Primary PREPL deficiency like Blood</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>muscle biopsy</intervention_name>
    <description>Muscle biopsy during planned anesthesia/surgery</description>
    <arm_group_label>Control muscle</arm_group_label>
    <arm_group_label>Prader-Willli syndrome muscle</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  According to group&#xD;
&#xD;
          -  Control group: children seen at a postinfectious consultation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Control group: symptoms overlapping with PREPL deficiency, genetic or syndromic&#xD;
             disease, atypically developing children&#xD;
&#xD;
          -  other groups: contraindication for blood draw&#xD;
&#xD;
          -  group with muscle biopsy: contra-indication for muscle biopsy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Luc Régal, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>KU Leuven</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Luc Régal, MD</last_name>
    <phone>003216343820</phone>
    <email>luc.regal@uzleuven.be</email>
  </overall_contact>
  <location>
    <facility>
      <name>UZLeuven</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <contact>
      <last_name>Luc Régal, MD</last_name>
      <phone>003216343820</phone>
      <email>Luc.regal@uzleuven.be</email>
    </contact>
    <investigator>
      <last_name>Luc Régal, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <reference>
    <citation>Regal L, Shen XM, Selcen D, Verhille C, Meulemans S, Creemers JW, Engel AG. PREPL deficiency with or without cystinuria causes a novel myasthenic syndrome. Neurology. 2014 Apr 8;82(14):1254-60. doi: 10.1212/WNL.0000000000000295. Epub 2014 Mar 7.</citation>
    <PMID>24610330</PMID>
  </reference>
  <reference>
    <citation>Jaeken J, Martens K, Francois I, Eyskens F, Lecointre C, Derua R, Meulemans S, Slootstra JW, Waelkens E, de Zegher F, Creemers JW, Matthijs G. Deletion of PREPL, a gene encoding a putative serine oligopeptidase, in patients with hypotonia-cystinuria syndrome. Am J Hum Genet. 2006 Jan;78(1):38-51. doi: 10.1086/498852. Epub 2005 Nov 23.</citation>
    <PMID>16385448</PMID>
  </reference>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>October 1, 2014</study_first_submitted>
  <study_first_submitted_qc>October 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 13, 2014</study_first_posted>
  <last_update_submitted>October 13, 2014</last_update_submitted>
  <last_update_submitted_qc>October 13, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 15, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dwarfism</mesh_term>
    <mesh_term>Dwarfism, Pituitary</mesh_term>
    <mesh_term>Prader-Willi Syndrome</mesh_term>
    <mesh_term>Muscle Hypotonia</mesh_term>
    <mesh_term>Cystinuria</mesh_term>
    <mesh_term>Syndrome</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/NCT02263781
org study id: S57206
nct id: NCT02263781
lead sponsor: 
collaborator: 
has dmc: No
Evaluation of PREPL activity in healthy controls and known or possible PREPL deficient
      patients
PREPL is defective in hypotonia cystinuria syndrome and in isolated PREPL deficiency. The
      investigators have constructed a blood test to evaluate PREPL activity in patients with
      possible PREPL deficiency.

      The study will determine normal values for age (0-18) for PREPL activity in blood.

      Also, patients with a clinical phenotype that overlaps with PREPL deficiency (including
      patients with known primary PREPL deficiency and Prader-Willi syndrome) will be evaluated for
      PREPL activity in blood.

      A last part of the study will involve muscle biopsies during elective anesthesia/surgery for
      other reasons. There will be 2 groups: patients without signs of PREPL deficiency undergoing
      surgery (controls) and patients with Prader-Willi syndrome undergoing anesthesia or surgery
      (patients). The control group will be age-matched to the hypotonia group. In the muscle
      biopsies, PREPL activity and expression will be evaluated.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: PREPL activity (ng active PREPL/g protein) normal values in blood
time frame: 3 months
description: normal values for PREPL activity
measure: PREPL activity in patients with Prader Willi syndrome compared to activity in normal controls
time frame: 3 months
description: Comparison of PREPL activity in blood and muscle between above mentioned groups
measure: PREPL activity in patients with primary PREPL deficiency compared to activity in normal controls
time frame: 3 months
description: Comparison of PREPL activity in blood between above mentioned groups
measure: PREPL activity in patients with muscle weakness/obesity/growth hormone deficiency compared to activity in normal controls
time frame: 3 months
description: exploratory evaluation
arm group label: Control Blood
arm group type: Experimental
description: Patients on routine postinfectious control, blood draw
arm group label: Primary PREPL deficiency Blood
arm group type: Experimental
description: Patients with primary PREPL deficiency, blood draw
arm group label: Prader Willi syndrome Blood
arm group type: Experimental
description: Patients with Prader-Willi syndrome, blood draw
arm group label: Primary PREPL deficiency like Blood
arm group type: Experimental
description: Patients with symptoms overlapping with primary PREPL deficiency (like hypotonia, growth hormone deficiency, obesity), blood draw
arm group label: Control muscle
arm group type: Experimental
description: Patients without hypotonia, growth hormone deficiency, obesity, undergoing elective surgery, muscle biopsy from the surgical site and blood draw
arm group label: Prader-Willli syndrome muscle
arm group type: Experimental
description: Patients with Prader-Willi syndrome undergoing elective anesthesia or surgery, muscle biopsy (from surgical site if applicable) and blood draw
intervention type: Procedure
intervention name: Blood draw
description: Blood draw
arm group label: Control Blood
arm group label: Control muscle
arm group label: Prader Willi syndrome Blood
arm group label: Prader-Willli syndrome muscle
arm group label: Primary PREPL deficiency Blood
arm group label: Primary PREPL deficiency like Blood
intervention type: Procedure
intervention name: muscle biopsy
description: Muscle biopsy during planned anesthesia/surgery
arm group label: Control muscle
arm group label: Prader-Willli syndrome muscle
criteria: 
gender: All
minimum age: N/A
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Luc Régal, MD
role: Principal Investigator
affiliation: KU Leuven
last name: Luc Régal, MD
phone: 003216343820
email: luc.regal@uzleuven.be
facility: 
contact: 
investigator: 
country: Belgium
citation: Regal L, Shen XM, Selcen D, Verhille C, Meulemans S, Creemers JW, Engel AG. PREPL deficiency with or without cystinuria causes a novel myasthenic syndrome. Neurology. 2014 Apr 8;82(14):1254-60. doi: 10.1212/WNL.0000000000000295. Epub 2014 Mar 7.
PMID: 24610330
citation: Jaeken J, Martens K, Francois I, Eyskens F, Lecointre C, Derua R, Meulemans S, Slootstra JW, Waelkens E, de Zegher F, Creemers JW, Matthijs G. Deletion of PREPL, a gene encoding a putative serine oligopeptidase, in patients with hypotonia-cystinuria syndrome. Am J Hum Genet. 2006 Jan;78(1):38-51. doi: 10.1086/498852. Epub 2005 Nov 23.
PMID: 16385448
responsible party type: Sponsor
mesh term: Dwarfism
mesh term: Dwarfism, Pituitary
mesh term: Prader-Willi Syndrome
mesh term: Muscle Hypotonia
mesh term: Cystinuria
mesh term: Syndrome