<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/NCT03785275</url>
  </required_header>
  <id_info>
    <org_study_id>NL59582.091.17</org_study_id>
    <nct_id>NCT03785275</nct_id>
  </id_info>
  <brief_title>Beta Cell Imaging in T1D Patients With a Different Glycemic Control</brief_title>
  <acronym>GLP1-reg</acronym>
  <official_title>Beta Cell Imaging in Type 1 Diabetes With Stable Near-normal and Unstable Glucose Control Using PET</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Radboud University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </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 aim of this study is to measure (residual) beta cell mass in type 1 diabetes&#xD;
      (T1D) patients with stable near-normal and unstable glucose control using PET/CT imaging, to&#xD;
      improve the understanding of the relation between beta cell mass and glycemic control in T1D.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Type 1 diabetes (T1D) is characterized by a progressive decrease in beta cell function due to&#xD;
      an autoimmune attack on the beta cells, which will lead to a reduction in insulin secretion.&#xD;
      Endogenous insulin secretion can be determined measuring C-peptide, which is secreted in&#xD;
      equal amounts to insulin. The loss of insulin secretion, indicated by an immeasurable&#xD;
      C-peptide level, will hamper glycemic control which results in increased glycated haemoglobin&#xD;
      (HbA1c) levels. Also, hypoglycemic events can occur more frequently. Initially, the belief&#xD;
      was that this could be explained by the loss of all pancreatic beta cells due to the&#xD;
      autoimmune attack. However, recent literature suggests that a considerable number of beta&#xD;
      cells can survive this attack. This could mean that certain beta cells survived, but have&#xD;
      lost their function. The ratio of functional and non-functional residual beta cells might&#xD;
      play an important role in the degree of glycemic control. It would therefore be of great&#xD;
      interest to study residual beta cell mass in two types of T1D patients that differ in&#xD;
      glycemic control. Although both types of patients receive treatment, one group of patients is&#xD;
      characterized by a stable near-normal glucose control while the second group is characterized&#xD;
      by an unstable glucose control. In case glycemic control mostly depends on beta cell function&#xD;
      and less on beta cell mass, novel therapies could focus on the functional reactivation of&#xD;
      these non-functional beta cells to restore overall beta cell function. This could especially&#xD;
      be in favour of patients with an unstable glucose control. Beta cell mass will be determined&#xD;
      using Ga-68-NODAGA-exendin-4 positron emission tomography (PET), which allows visualization&#xD;
      of pancreatic beta cells as well as absolute quantification of tracer uptake, providing a&#xD;
      measure for the pancreatic beta cell mass. The outcome of this study will lead to a better&#xD;
      understanding of the relation between the amount of residual beta cells, beta cell function&#xD;
      and the influence of glycemic control. This could provide new insights regarding the&#xD;
      development of new therapies to improve beta cell function and glycemic control, which could&#xD;
      lower disease burden and improve the patient's quality of life.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    It was not possible to include 9 study participants with unstable glucose in due time, and&#xD;
    therefore 7 individuals with unstable glucose control were included.&#xD;
  </why_stopped>
  <start_date type="Actual">December 6, 2017</start_date>
  <completion_date type="Actual">November 9, 2020</completion_date>
  <primary_completion_date type="Actual">November 9, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Beta cell mass</measure>
    <time_frame>2 years</time_frame>
    <description>Pancreatic uptake of the tracer is measured by quantitative analysis (measure for beta cell mass)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Beta cell mass vs. beta cell function</measure>
    <time_frame>2 years</time_frame>
    <description>The correlation of the measured beta cell mass to the beta cell function</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">16</enrollment>
  <condition>Type 1 Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>Subjects with stable near-normal T1D</arm_group_label>
    <description>Mixed-meal tolerance test&#xD;
Intravenous injection with gallium-68-exendin followed by a PET/CT scan</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Subjects with unstable T1D</arm_group_label>
    <description>Mixed-meal tolerance test&#xD;
Intravenous injection with gallium-68-exendin followed by a PET/CT scan</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>gallium-68-exendin PET/CT</intervention_name>
    <description>PET/CT scan after injection with gallium-68-exendin</description>
    <arm_group_label>Subjects with stable near-normal T1D</arm_group_label>
    <arm_group_label>Subjects with unstable T1D</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        The study population will include 18 individuals with T1D for at least 1 year with a&#xD;
        minimum age of 18 years. This population consists of two groups that include 9 subjects&#xD;
        with stable near-normal glucose control and 9 individuals with unstable glucose control.&#xD;
        The differentiation between T1D patients with stable near-normal and unstable glucose&#xD;
        control will be based on their HbA1c value, the number of severe hypoglycemic events and&#xD;
        the patient's hypoglycaemic awareness.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Group 1 (stable glycemic control)&#xD;
&#xD;
          -  Age ≥18 years&#xD;
&#xD;
          -  T1D diagnosed ≥1 year at the start of the study&#xD;
&#xD;
          -  HbA1c &lt;7 (&lt;53 mmol/mol)&#xD;
&#xD;
          -  17≤ BMI ≤30 kg/m2&#xD;
&#xD;
          -  No severe hypoglycemic events in the past year and a maximum of 2 severe hypoglycemic&#xD;
             events in their entire life.&#xD;
&#xD;
          -  Intact hypoglycemic awareness&#xD;
&#xD;
          -  Ability to sign informed consent&#xD;
&#xD;
        Group 2 (unstable glycemic control) Age ≥18 years&#xD;
&#xD;
          -  T1D diagnosed ≥1 year at the start of the study&#xD;
&#xD;
          -  HbA1c &gt;8.5 (&gt;69 mmol/mol)&#xD;
&#xD;
          -  17≤ BMI ≤30 kg/m2&#xD;
&#xD;
          -  Minimum of 2 severe hypoglycemic events in the past year, or an impaired awareness of&#xD;
             hypoglycemia (subjects may comply with both criteria, but this is not a requirement)&#xD;
&#xD;
          -  Ability to sign informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous treatment (within 6 months) with synthetic Exendin (Exenatide, Byetta®) or&#xD;
             Dipeptidyl-Peptidase IV inhibitors&#xD;
&#xD;
          -  Liver disease&#xD;
&#xD;
          -  Renal disease&#xD;
&#xD;
          -  Pregnancy or the wish to become pregnant within 6 months after the study&#xD;
&#xD;
          -  Breastfeeding&#xD;
&#xD;
          -  BMI &lt;17 kg/m2 or BMI &gt;30 kg/m2&#xD;
&#xD;
          -  Age &lt;18 years&#xD;
&#xD;
          -  Inability to sign informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Radboudumc</name>
      <address>
        <city>Nijmegen</city>
        <state>Gelderland</state>
        <zip>6525 GA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>December 20, 2018</study_first_submitted>
  <study_first_submitted_qc>December 21, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 24, 2018</study_first_posted>
  <last_update_submitted>January 29, 2022</last_update_submitted>
  <last_update_submitted_qc>January 29, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Glycemic control</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus, Type 1</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/NCT03785275
org study id: NL59582.091.17
nct id: NCT03785275
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The primary aim of this study is to measure (residual) beta cell mass in type 1 diabetes
      (T1D) patients with stable near-normal and unstable glucose control using PET/CT imaging, to
      improve the understanding of the relation between beta cell mass and glycemic control in T1D.
Type 1 diabetes (T1D) is characterized by a progressive decrease in beta cell function due to
      an autoimmune attack on the beta cells, which will lead to a reduction in insulin secretion.
      Endogenous insulin secretion can be determined measuring C-peptide, which is secreted in
      equal amounts to insulin. The loss of insulin secretion, indicated by an immeasurable
      C-peptide level, will hamper glycemic control which results in increased glycated haemoglobin
      (HbA1c) levels. Also, hypoglycemic events can occur more frequently. Initially, the belief
      was that this could be explained by the loss of all pancreatic beta cells due to the
      autoimmune attack. However, recent literature suggests that a considerable number of beta
      cells can survive this attack. This could mean that certain beta cells survived, but have
      lost their function. The ratio of functional and non-functional residual beta cells might
      play an important role in the degree of glycemic control. It would therefore be of great
      interest to study residual beta cell mass in two types of T1D patients that differ in
      glycemic control. Although both types of patients receive treatment, one group of patients is
      characterized by a stable near-normal glucose control while the second group is characterized
      by an unstable glucose control. In case glycemic control mostly depends on beta cell function
      and less on beta cell mass, novel therapies could focus on the functional reactivation of
      these non-functional beta cells to restore overall beta cell function. This could especially
      be in favour of patients with an unstable glucose control. Beta cell mass will be determined
      using Ga-68-NODAGA-exendin-4 positron emission tomography (PET), which allows visualization
      of pancreatic beta cells as well as absolute quantification of tracer uptake, providing a
      measure for the pancreatic beta cell mass. The outcome of this study will lead to a better
      understanding of the relation between the amount of residual beta cells, beta cell function
      and the influence of glycemic control. This could provide new insights regarding the
      development of new therapies to improve beta cell function and glycemic control, which could
      lower disease burden and improve the patient's quality of life.
observational model: Case-Control
time perspective: Cross-Sectional
measure: Beta cell mass
time frame: 2 years
description: Pancreatic uptake of the tracer is measured by quantitative analysis (measure for beta cell mass)
measure: Beta cell mass vs. beta cell function
time frame: 2 years
description: The correlation of the measured beta cell mass to the beta cell function
arm group label: Subjects with stable near-normal T1D
description: Mixed-meal tolerance test
Intravenous injection with gallium-68-exendin followed by a PET/CT scan
arm group label: Subjects with unstable T1D
description: Mixed-meal tolerance test
Intravenous injection with gallium-68-exendin followed by a PET/CT scan
intervention type: Radiation
intervention name: gallium-68-exendin PET/CT
description: PET/CT scan after injection with gallium-68-exendin
arm group label: Subjects with stable near-normal T1D
arm group label: Subjects with unstable T1D
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Netherlands
responsible party type: Sponsor
mesh term: Diabetes Mellitus, Type 1