<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/NCT02211742</url>
  </required_header>
  <id_info>
    <org_study_id>CUI_001</org_study_id>
    <nct_id>NCT02211742</nct_id>
  </id_info>
  <brief_title>Dapagliflozin in Type 1 Diabetes</brief_title>
  <acronym>DapaT1DM</acronym>
  <official_title>Short-term Effects of Dapagliflozin on Fasting and Postprandial Glucose Homeostasis in Male Type 1 Diabetes Patients.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University Innsbruck</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Medical University of Graz</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Bern</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Medical University Innsbruck</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Dapagliflozin is a highly selective, reversible and potent inhibitor of the&#xD;
      sodium-glucose-linked Transporter 2 (SGLT2), which was successfully investigated for its use&#xD;
      as a treatment option in type 2 diabetes mellitus. The effect of dapagliflozin is an&#xD;
      increased glucosuria, and it was shown that mean blood glucose concentrations and&#xD;
      postprandial glucose excursion in special were significantly reduced in type 2 diabetic&#xD;
      patients. Due to its mechanism-of action it seems likely that also type 1 diabetic patients&#xD;
      will benefit from dapagliflozin. The present study is focused on the effects of dapagliflozin&#xD;
      on fasting glucose homeostasis and postprandial glucose excursion in male type 1diabetic&#xD;
      patients. Participants will subsequently receive 10 milligrams of dapagliflozin and placebo&#xD;
      for 3 days (equals 2 x 30mg per cross-over period) in a double-blind, randomised, cross-over&#xD;
      design. The effects will be measured via euglycemic hyperinsulinemic clamp studies (fasting&#xD;
      glucose homeostasis) and euglycemic oral glucose tolerance clamp tests (postprandial glucose&#xD;
      excursions).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 2014</start_date>
  <completion_date type="Actual">February 8, 2017</completion_date>
  <primary_completion_date type="Actual">July 29, 2016</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>fasting glucose homeostasis</measure>
    <time_frame>study visit, immediatly</time_frame>
    <description>During hyperinsulinemic, euglycemic clamp studies, fasting glucose homeostasis will be determined for both, dapagliflozin and placebo.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>postprandial glucose homeostasis</measure>
    <time_frame>study visit, immediatly</time_frame>
    <description>During euglycemic oral glucose tolerance clamp tests, postprandial glucose excursion will be determined and compared between dapagliflozin and placebo.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Fasting Glucose</condition>
  <condition>Glucose Excursion</condition>
  <condition>Glycemic Control</condition>
  <arm_group>
    <arm_group_label>dapagliflozin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>10mg dapagliflozin per 24h for 3 days per cross-over phase (equals 2 x 30mg)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo sugar pills</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>placebo tablet, 1 per 24h for 3 days in total per cross-over phase (equals 2 x 3 tablets)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dapagliflozin</intervention_name>
    <description>euglycemic hyperinsulinemic clamp tests and euglycemic oral glucose tolerance clamp tests after the short-term (i.e.: 3 days, equals 10mg / 24h) intake of dapagliflozin</description>
    <arm_group_label>dapagliflozin</arm_group_label>
    <arm_group_label>placebo sugar pills</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Type 1 diabetes mellitus (duration of disease at least 5 years)&#xD;
&#xD;
          -  C-peptide concentration &lt; 0.2µg/l&#xD;
&#xD;
          -  male sex&#xD;
&#xD;
          -  aged 18 to 60 years&#xD;
&#xD;
          -  Body Mass Index 20 - 25 kg/m2&#xD;
&#xD;
          -  no measurable, clinically relevant ketonuria&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  insufficient venous status on both forearms&#xD;
&#xD;
          -  renal and/or hepatic insufficiency (including microalbuminuria and/or&#xD;
             albumin/creatinin-ratio)&#xD;
&#xD;
          -  history of cancer&#xD;
&#xD;
          -  intake of medication and/or substances capable to influence insulin sensitivity within&#xD;
             the last 3 months prior to study inclusion&#xD;
&#xD;
          -  alcohol- and/or drug abuse, nicotine consumption &gt; 5 cigarettes / 24h&#xD;
&#xD;
          -  brittle-diabetes&#xD;
&#xD;
          -  history of severe hypoglycemia, defined as the need for foreign assistance independent&#xD;
             of actual blood glucose concentration measured&#xD;
&#xD;
          -  history or evidence of any other clinically significant disorder, condition or disease&#xD;
             other than those outlined above that, in the opinion of the investigator may&#xD;
             compromise the ability of the participant to give written informed consent, would pose&#xD;
             a risk to subject safety, or interfere with the study evaluation, procedures or&#xD;
             completion.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Markus Laimer, PD MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical University Innsbruck, Department of Internal Medicine I</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Medical University Innsbruck, Department of Internal Medicine I</name>
      <address>
        <city>Innsbruck</city>
        <state>Tirol</state>
        <zip>6020</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
  </location_countries>
  <reference>
    <citation>DeFronzo RA, Hompesch M, Kasichayanula S, Liu X, Hong Y, Pfister M, Morrow LA, Leslie BR, Boulton DW, Ching A, LaCreta FP, Griffen SC. Characterization of renal glucose reabsorption in response to dapagliflozin in healthy subjects and subjects with type 2 diabetes. Diabetes Care. 2013 Oct;36(10):3169-76. doi: 10.2337/dc13-0387. Epub 2013 Jun 4.</citation>
    <PMID>23735727</PMID>
  </reference>
  <reference>
    <citation>Abdul-Ghani MA, DeFronzo RA. Dapagliflozin for the treatment of type 2 diabetes. Expert Opin Pharmacother. 2013 Aug;14(12):1695-703. doi: 10.1517/14656566.2013.812632. Epub 2013 Jun 26.</citation>
    <PMID>23800130</PMID>
  </reference>
  <reference>
    <citation>Mather A, Pollock C. Glucose handling by the kidney. Kidney Int Suppl. 2011 Mar;(120):S1-6. doi: 10.1038/ki.2010.509.</citation>
    <PMID>21358696</PMID>
  </reference>
  <reference>
    <citation>Plosker GL. Dapagliflozin: a review of its use in type 2 diabetes mellitus. Drugs. 2012 Dec 3;72(17):2289-312. doi: 10.2165/11209910-000000000-00000.</citation>
    <PMID>23170914</PMID>
  </reference>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>August 6, 2014</study_first_submitted>
  <study_first_submitted_qc>August 6, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 7, 2014</study_first_posted>
  <last_update_submitted>March 14, 2023</last_update_submitted>
  <last_update_submitted_qc>March 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 16, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University Innsbruck</investigator_affiliation>
    <investigator_full_name>Markus Laimer</investigator_full_name>
    <investigator_title>PD MD</investigator_title>
  </responsible_party>
  <keyword>dapagliflozin</keyword>
  <keyword>fasting glucose</keyword>
  <keyword>postprandial glucose excursion</keyword>
  <keyword>euglycemic hyperinsulinemic clamp</keyword>
  <keyword>euglycemic oral glucose tolerance test</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus, Type 1</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dapagliflozin</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/NCT02211742
org study id: CUI_001
nct id: NCT02211742
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
Dapagliflozin is a highly selective, reversible and potent inhibitor of the
      sodium-glucose-linked Transporter 2 (SGLT2), which was successfully investigated for its use
      as a treatment option in type 2 diabetes mellitus. The effect of dapagliflozin is an
      increased glucosuria, and it was shown that mean blood glucose concentrations and
      postprandial glucose excursion in special were significantly reduced in type 2 diabetic
      patients. Due to its mechanism-of action it seems likely that also type 1 diabetic patients
      will benefit from dapagliflozin. The present study is focused on the effects of dapagliflozin
      on fasting glucose homeostasis and postprandial glucose excursion in male type 1diabetic
      patients. Participants will subsequently receive 10 milligrams of dapagliflozin and placebo
      for 3 days (equals 2 x 30mg per cross-over period) in a double-blind, randomised, cross-over
      design. The effects will be measured via euglycemic hyperinsulinemic clamp studies (fasting
      glucose homeostasis) and euglycemic oral glucose tolerance clamp tests (postprandial glucose
      excursions).
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: fasting glucose homeostasis
time frame: study visit, immediatly
description: During hyperinsulinemic, euglycemic clamp studies, fasting glucose homeostasis will be determined for both, dapagliflozin and placebo.
measure: postprandial glucose homeostasis
time frame: study visit, immediatly
description: During euglycemic oral glucose tolerance clamp tests, postprandial glucose excursion will be determined and compared between dapagliflozin and placebo.
arm group label: dapagliflozin
arm group type: Active Comparator
description: 10mg dapagliflozin per 24h for 3 days per cross-over phase (equals 2 x 30mg)
arm group label: placebo sugar pills
arm group type: Placebo Comparator
description: placebo tablet, 1 per 24h for 3 days in total per cross-over phase (equals 2 x 3 tablets)
intervention type: Drug
intervention name: Dapagliflozin
description: euglycemic hyperinsulinemic clamp tests and euglycemic oral glucose tolerance clamp tests after the short-term (i.e.: 3 days, equals 10mg / 24h) intake of dapagliflozin
arm group label: dapagliflozin
arm group label: placebo sugar pills
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Markus Laimer, PD MD
role: Principal Investigator
affiliation: Medical University Innsbruck, Department of Internal Medicine I
facility: 
country: Austria
citation: DeFronzo RA, Hompesch M, Kasichayanula S, Liu X, Hong Y, Pfister M, Morrow LA, Leslie BR, Boulton DW, Ching A, LaCreta FP, Griffen SC. Characterization of renal glucose reabsorption in response to dapagliflozin in healthy subjects and subjects with type 2 diabetes. Diabetes Care. 2013 Oct;36(10):3169-76. doi: 10.2337/dc13-0387. Epub 2013 Jun 4.
PMID: 23735727
citation: Abdul-Ghani MA, DeFronzo RA. Dapagliflozin for the treatment of type 2 diabetes. Expert Opin Pharmacother. 2013 Aug;14(12):1695-703. doi: 10.1517/14656566.2013.812632. Epub 2013 Jun 26.
PMID: 23800130
citation: Mather A, Pollock C. Glucose handling by the kidney. Kidney Int Suppl. 2011 Mar;(120):S1-6. doi: 10.1038/ki.2010.509.
PMID: 21358696
citation: Plosker GL. Dapagliflozin: a review of its use in type 2 diabetes mellitus. Drugs. 2012 Dec 3;72(17):2289-312. doi: 10.2165/11209910-000000000-00000.
PMID: 23170914
responsible party type: Principal Investigator
investigator affiliation: Medical University Innsbruck
investigator full name: Markus Laimer
investigator title: PD MD
mesh term: Diabetes Mellitus, Type 1
mesh term: Dapagliflozin