<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/NCT03768518</url>
  </required_header>
  <id_info>
    <org_study_id>NL54275.091.15</org_study_id>
    <nct_id>NCT03768518</nct_id>
  </id_info>
  <brief_title>GLP-1 Receptor Expression in CHI</brief_title>
  <acronym>GLP-1-CHI</acronym>
  <official_title>The Physiology of Glucagon-like-peptide-1 Espression in Patients With Endogenous Hyperinsulinism: Correlation With Histopathology</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Radboud University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>European Commission</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University College, London</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Charite University, Berlin, Germany</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital, Basel, Switzerland</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Insel Gruppe AG, University Hospital Bern</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Helsinki</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Turku University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Medical Center Groningen</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Radboud University Medical Center</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>
      The primary objective is the in vivo and ex vivo investigation of the expression and&#xD;
      distribution of the GLP-1R in the pancreas of CHI patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Congenital hyperinsulinism (CHI) is a rare disease of infants characterized by the presence&#xD;
      of functionally defective non-neoplastic beta-cells with inappropriate (over-) secretion of&#xD;
      insulin, leading to life-threatening hypoglycaemia. Beta cells specifically express the&#xD;
      glucagon-like-peptide-1 (GLP-1R), which could be a promising target for diagnostic and&#xD;
      therapeutic purposes. In this study we propose to investigate the physiology of GLP-1&#xD;
      receptor expression in CHI. Expression of the GLP-1 receptor will be quantified in vivo by&#xD;
      68Ga-NODAGA-exendin-4 PET/CT. This data will be compared with post-surgical autoradiography&#xD;
      and morphometric determinations.&#xD;
&#xD;
      Furthermore, we will evaluate 68Ga-exendin-4 PET/CT for the pre-operative localization of&#xD;
      foci of over-secreting beta cells in CHI and the discrimination between focal and diffuse&#xD;
      CHI. We will compare GLP-1R PET/CT to the currently used pre-operative imaging technique&#xD;
      (18F-DOPA PET combined with contrast enhanced CT). To compare these imaging techniques&#xD;
      according to sensitivity, we will analyze intra-operative findings and clinical outcomes.&#xD;
&#xD;
      These highly relevant data will allow us to evaluate the expression of GLP-1R in CHI and its&#xD;
      usefulness as a target for diagnosis of this disease. Since the localization of foci in CHI&#xD;
      and the discrimination between focal and diffuse CHI is challenging, surgical removal of&#xD;
      unnecessary large portions of the pancreas in frequently necessary. Evaluation of a better&#xD;
      target for pre-operative imaging would therefore be of great value.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      The primary objective is the in vivo and ex vivo investigation of the expression and&#xD;
      distribution of the GLP-1R in the pancreas of CHI patients. A 68Ga-NODAGA-exendin 4 PET/CT&#xD;
      will be performed in all patients included in this study. The results of quantitative imaging&#xD;
      will then be compared to GLP-1R expression and autoradiography of surgical specimens to&#xD;
      determine the interdependency of radiotracer uptake, beta cell mass and GLP-1R expression.&#xD;
&#xD;
      Furthermore, GLP-1R imaging will be compared to the standard imaging techniques now used in&#xD;
      pre-operative imaging of children with CHI. All patients will undergo the standard imaging&#xD;
      procedure, consisting of an 18F-DOPA PET scan combined with a contrast-enhanced CT. The&#xD;
      results of the GLP-1R imaging will be compared to standard imaging in respect to sensitivity&#xD;
      for localization of the lesion and discrimination between focal and diffuse CHI. This will be&#xD;
      determined by the comparison of the results of pre-operative imaging with intra-operative&#xD;
      findings.&#xD;
&#xD;
      Also, the safety (side-effects) of 68Ga-NODAGA-exendin and 18F-DOPA will be assessed.&#xD;
&#xD;
      Furthermore, dosimetric calculations will be performed and the minimum radioactivity dose of&#xD;
      68Ga-NODAGA-exendin 4 to obtain acceptable/reliable images will be determined.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">February 7, 2018</start_date>
  <completion_date type="Anticipated">February 1, 2019</completion_date>
  <primary_completion_date type="Anticipated">February 1, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Expression and distribution of GLP-1R in pancreas of children with CHI</measure>
    <time_frame>1 year</time_frame>
    <description>Comparison of PET quantification with autoradiography and histology</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Comparison of the exendin PET/CT and F-DOPA PET/CT</measure>
    <time_frame>1 year</time_frame>
    <description>Comparison of sensitivity and specificity for localization of focal CHI</description>
  </secondary_outcome>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Congenital Hyperinsulinism</condition>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>68Ga-exendin-4 PET/CT</intervention_name>
    <description>68Ga-exendin-4 PET/CT</description>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Tumour tissue&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        patients (&lt;16 years) with biochemically proven endogenous congenital hyperinsulinism&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Biochemically and clinically proven endogenous congenital hyperinsulinism:&#xD;
&#xD;
          -  Unresponsive to medical treatment (diazoxide)&#xD;
&#xD;
          -  Indication for 18F-DOPA PET/CT based on mutation analysis&#xD;
&#xD;
          -  Standard imaging (18F-DOPA PET/CT) not older than 8 weeks&#xD;
&#xD;
          -  &lt;16 years old&#xD;
&#xD;
          -  Informed consent signed by parents or legal guardians of the patient.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Genetically proven diffuse CHI (presenting with a homozygous or compound heterozygous&#xD;
             ABCC8/KCNJ11 mutation)&#xD;
&#xD;
          -  Calculated creatinine clearance below 40 ml/min&#xD;
&#xD;
          -  Evidence of other malignancy than insulin producing tumors in conventional imaging&#xD;
             (suspicious liver, bone and lung lesions based on CT)&#xD;
&#xD;
          -  Age &gt; 16 years&#xD;
&#xD;
          -  No signed informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>16 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Martin Gotthardt, Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Radboud University Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Marti Boss</last_name>
    <phone>+31243667243</phone>
    <email>marti.boss@radboudumc.nl</email>
  </overall_contact>
  <location>
    <facility>
      <name>Radboudumc</name>
      <address>
        <city>Nijmegen</city>
        <zip>6500HB</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marti Boss</last_name>
      <phone>+31243667243</phone>
      <email>marti.boss@radboudumc.nl</email>
    </contact>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>July 11, 2018</study_first_submitted>
  <study_first_submitted_qc>December 6, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 7, 2018</study_first_posted>
  <last_update_submitted>December 6, 2018</last_update_submitted>
  <last_update_submitted_qc>December 6, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 7, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Radboud University Medical Center</investigator_affiliation>
    <investigator_full_name>Martin Gotthardt</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Exendin</keyword>
  <keyword>GLP-1</keyword>
  <keyword>PET/CT</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Congenital Hyperinsulinism</mesh_term>
    <mesh_term>Nesidioblastosis</mesh_term>
    <mesh_term>Hyperinsulinism</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Exenatide</mesh_term>
  </intervention_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/NCT03768518
org study id: NL54275.091.15
nct id: NCT03768518
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The primary objective is the in vivo and ex vivo investigation of the expression and
      distribution of the GLP-1R in the pancreas of CHI patients.
Congenital hyperinsulinism (CHI) is a rare disease of infants characterized by the presence
      of functionally defective non-neoplastic beta-cells with inappropriate (over-) secretion of
      insulin, leading to life-threatening hypoglycaemia. Beta cells specifically express the
      glucagon-like-peptide-1 (GLP-1R), which could be a promising target for diagnostic and
      therapeutic purposes. In this study we propose to investigate the physiology of GLP-1
      receptor expression in CHI. Expression of the GLP-1 receptor will be quantified in vivo by
      68Ga-NODAGA-exendin-4 PET/CT. This data will be compared with post-surgical autoradiography
      and morphometric determinations.

      Furthermore, we will evaluate 68Ga-exendin-4 PET/CT for the pre-operative localization of
      foci of over-secreting beta cells in CHI and the discrimination between focal and diffuse
      CHI. We will compare GLP-1R PET/CT to the currently used pre-operative imaging technique
      (18F-DOPA PET combined with contrast enhanced CT). To compare these imaging techniques
      according to sensitivity, we will analyze intra-operative findings and clinical outcomes.

      These highly relevant data will allow us to evaluate the expression of GLP-1R in CHI and its
      usefulness as a target for diagnosis of this disease. Since the localization of foci in CHI
      and the discrimination between focal and diffuse CHI is challenging, surgical removal of
      unnecessary large portions of the pancreas in frequently necessary. Evaluation of a better
      target for pre-operative imaging would therefore be of great value.

      Objective:

      The primary objective is the in vivo and ex vivo investigation of the expression and
      distribution of the GLP-1R in the pancreas of CHI patients. A 68Ga-NODAGA-exendin 4 PET/CT
      will be performed in all patients included in this study. The results of quantitative imaging
      will then be compared to GLP-1R expression and autoradiography of surgical specimens to
      determine the interdependency of radiotracer uptake, beta cell mass and GLP-1R expression.

      Furthermore, GLP-1R imaging will be compared to the standard imaging techniques now used in
      pre-operative imaging of children with CHI. All patients will undergo the standard imaging
      procedure, consisting of an 18F-DOPA PET scan combined with a contrast-enhanced CT. The
      results of the GLP-1R imaging will be compared to standard imaging in respect to sensitivity
      for localization of the lesion and discrimination between focal and diffuse CHI. This will be
      determined by the comparison of the results of pre-operative imaging with intra-operative
      findings.

      Also, the safety (side-effects) of 68Ga-NODAGA-exendin and 18F-DOPA will be assessed.

      Furthermore, dosimetric calculations will be performed and the minimum radioactivity dose of
      68Ga-NODAGA-exendin 4 to obtain acceptable/reliable images will be determined.
observational model: Case-Only
time perspective: Prospective
measure: Expression and distribution of GLP-1R in pancreas of children with CHI
time frame: 1 year
description: Comparison of PET quantification with autoradiography and histology
measure: Comparison of the exendin PET/CT and F-DOPA PET/CT
time frame: 1 year
description: Comparison of sensitivity and specificity for localization of focal CHI
intervention type: Diagnostic Test
intervention name: 68Ga-exendin-4 PET/CT
description: 68Ga-exendin-4 PET/CT
Tumour tissue
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: 16 Years
healthy volunteers: No
last name: Martin Gotthardt, Prof.
role: Principal Investigator
affiliation: Radboud University Medical Center
last name: Marti Boss
phone: +31243667243
email: marti.boss@radboudumc.nl
facility: 
status: Recruiting
contact: 
country: Netherlands
responsible party type: Principal Investigator
investigator affiliation: Radboud University Medical Center
investigator full name: Martin Gotthardt
investigator title: Professor
mesh term: Congenital Hyperinsulinism
mesh term: Nesidioblastosis
mesh term: Hyperinsulinism
mesh term: Exenatide