<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/NCT02987738</url>
  </required_header>
  <id_info>
    <org_study_id>ESR-15-11453</org_study_id>
    <nct_id>NCT02987738</nct_id>
  </id_info>
  <brief_title>Pilot Study to Explore the Efficacy of DAPAglifozin as add-on to Closed-loop Control in Patients With Type 1 Diabetes</brief_title>
  <acronym>DapaDream</acronym>
  <official_title>A Randomized, Double-Blind, Placebo-controlled, Single-center, Phase 1 Inpatient Pilot Study to Explore the Safety and Efficacy of DAPAglifozin as Add-on to Day and Night Closed-loop Control in Patients Type 1 Diabetes (T1D)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kinderkrankenhaus auf der Bult</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Alcedis GmbH</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Kinderkrankenhaus auf der Bult</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Dapagliflozin has a unique mechanism of action that does not directly affect either insulin&#xD;
      resistance or insulin secretion, but rather improves glycemia by reduction of glucose&#xD;
      re-absorption from proximal renal tubules. Dapagliflozin is expected to reduce mean daily&#xD;
      glucose, improve glycemic control and reduce overall insulin requirements. Improved glycemic&#xD;
      control with reduced variability may also lead to reduced frequency of hypoglycemia.&#xD;
&#xD;
      In youth with T1D, Dapagliflozin led to a significant reduction of insulin needed to achieve&#xD;
      target glucose irrespective of preexisting HbA1c levels.&#xD;
&#xD;
      In this pilot study data will be collected to investigate the effect on glucose of two doses&#xD;
      of 10mg (each) dapagliflozin within range for the ensuing 24 hours during the DreaMed&#xD;
      automated insulin delivery in patients with type 1 diabetes dosing with dapagliflozin in an&#xD;
      in-patient setting combined with an automated sensor based CE marked insulin delivery system&#xD;
      to data if dapagliflozin is a suitable add-on therapy. This will provide optimal monitoring&#xD;
      of subject safety and assessment of the effects of dapagliflozin in a structured setting.&#xD;
&#xD;
      If this inpatient study shows evidence that Dapagliflozin is a suitable add on therapy and&#xD;
      leads to an increase of time within the target glucose range when using a sensor based&#xD;
      insulin pump therapy (closed-loop) further outpatient studies are planned to be conducted.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this pilot study is to collect clinical data of two doses of 10mg (each)&#xD;
      dapagliflozin as add-on to night and day closed-loop control using the DreaMed automated&#xD;
      insulin delivery on the time [%] within glucose range 70-180 mg/dl (3.9-10mmol/l) for the&#xD;
      ensuing 24 hours with two oral mixed-meals.&#xD;
&#xD;
      The study aimed to patients who have different degrees of inadequate glycemic control despite&#xD;
      insulin use.&#xD;
&#xD;
      A maximum of 45 patients will be screened until 30 Type 1 Diabetes mellitus patient (15&#xD;
      adults, 15 adolescents) will completed the study.&#xD;
&#xD;
      The trial will consist of six visits: a screening visit (Visit 1), two dosing visits (Visit 2&#xD;
      and Visit 4), two phone visits (Visit 3 and Visit 5) and a follow-up visit (Visit 6).&#xD;
      Furthermore, an information visit will take place prior to the screening visit in order to&#xD;
      obtain patient's informed consent. Screening will take place 2-21 days prior to Visit 2 and&#xD;
      the follow-up visit will take place 5-21 days after the end of Visit 4. The dosing visits&#xD;
      will be separated by a wash-out period (5-30 days between the end of Visit 2 and begin of&#xD;
      Visit 4) during which the subjects will resume their normal insulin treatment. Each phone&#xD;
      visit (Visit 3 and Visit 5) will take place 3-5 days after the end of dosing Visits 2 and 4.&#xD;
      The planned total duration of the trial is 18-78 days per subject (rescheduled visits&#xD;
      excluded). Each subject will be randomised to a treatment sequence consisting of two&#xD;
      treatment periods in which the subjects will receive 2 times 10mg dapagliflozin and placebo&#xD;
      on two separate dosing visits.&#xD;
&#xD;
      Subjects metabolic control will be achieved by using the DreaMed system (closed loop). The&#xD;
      procedure will be used in order to aim and maintain blood glucose levels between 70 and 180&#xD;
      mg/dl thereby.&#xD;
&#xD;
      Two standardized mixed-meals will be given 12 hours and 18 hours after dosing. Blood glucose&#xD;
      measurements will be performed every 30min for 120min after the mixed-meal.&#xD;
&#xD;
      Blood samples for determination of dapagliflozin concentration in serum will be taken 14times&#xD;
      in 24hours as well as ß-Hydroxybutyrate and every urine sample will be collected for 24 hours&#xD;
      after first dosing for the determination of 24hour urinary glucose and creatinine for&#xD;
      efficacy measurement.&#xD;
&#xD;
      In addition a full blood gas analysis will be drawn if an elevated β-hydroxybutyrate of &gt;1.0&#xD;
      mmol/L will be detected.&#xD;
&#xD;
      24 hours after first dosing with dapagliflozin/ placebo of each dosing visit the subjects&#xD;
      will resume their usual insulin treatment and can leave the hospital.&#xD;
&#xD;
      After conclusion of the trial the documented insulin doses over time will be summed up for&#xD;
      calculation of the total insulin dose and the insulin dose per kg body weight per 24 hours.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 9, 2017</start_date>
  <completion_date type="Actual">December 19, 2017</completion_date>
  <primary_completion_date type="Actual">December 19, 2017</primary_completion_date>
  <phase>Phase 1</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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time in Range 70-180%</measure>
    <time_frame>24 hours</time_frame>
    <description>Collection of clinical data regarding the treatment of two doses of 10mg dapagliflozin as add-on to night and day closed-loop control using the DreaMed Algorithm and the time within glucose range 70-180 mg/dl (3.9-10mmol/l) [%]</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>urinary glucose excretion</measure>
    <time_frame>24 hours</time_frame>
    <description>effect on urinary glucose excretion after a treatment with two doses of 10mg dapagliflozin (1x10 mg before bedtime and 1x10mg in the morning) in patients with type 1 diabetes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>postprandial insulin need</measure>
    <time_frame>24 hours</time_frame>
    <description>effect of postprandial insulin need after Treatment with dapagliflozin</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ß-hydroxybutyrate</measure>
    <time_frame>24 hours</time_frame>
    <description>association between Treatment of dapagliflozin and ß-hydroxybutyrate levels</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction of Insulin dose</measure>
    <time_frame>24 hours</time_frame>
    <description>effect of insulin dose reduction during the DreaMed automated insulin delivery 24 hours after two doses of 10mg dapagliflozin in patients with type 1 diabetes</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Type1diabetes</condition>
  <arm_group>
    <arm_group_label>dapagliflozin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>two administrations of 10 mg dapagliflozin as tablet</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Oral Tablets</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>two administrations identical to the experimental drug</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dapagliflozin</intervention_name>
    <description>two administrations in the evening and 12 hours later</description>
    <arm_group_label>dapagliflozin</arm_group_label>
    <other_name>Forxiga</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Oral Tablet</intervention_name>
    <description>two administrations in the evening and 12 hours later</description>
    <arm_group_label>Placebo Oral Tablets</arm_group_label>
    <other_name>Control</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female aged 12-21 years (both inclusive)&#xD;
&#xD;
          2. Type 1 diabetes mellitus (as diagnosed clinically) ≥ 12 months&#xD;
&#xD;
          3. No DKA 12 weeks prior to the study&#xD;
&#xD;
          4. On CSII (insulin pump therapy) since at least 3 months&#xD;
&#xD;
          5. Average daily dose of Insulin between 0.6 - 2.0 U/kg&#xD;
&#xD;
          6. Body mass index 18 to 35 kg/m2 or the 10th to 99th centile for BMI according to age&#xD;
             and gender with a minimum weight of 50kg&#xD;
&#xD;
          7. A1c range 6,5% - 11% (inclusive)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of drug or alcohol abuse within the last five years prior to screening&#xD;
&#xD;
          2. Anamnestic history of hypersensitivity to the study drugs (or any component of the&#xD;
             study drug) or to drugs with similar chemical structures&#xD;
&#xD;
          3. History of severe or multiple allergies&#xD;
&#xD;
          4. Treatment with any other investigational drug within 3 months prior to screening&#xD;
&#xD;
          5. Progressive fatal disease&#xD;
&#xD;
          6. History of significant cardiovascular, respiratory, gastrointestinal, hepatic (ALAT&#xD;
             and/or ASAT &gt; 3 times the normal reference range), renal (creatinine &gt; 1.1 mg/dl in&#xD;
             women and &gt; 1.5 mg/dl in men), neurological, psychiatric and/or hematological disease&#xD;
             as judged by the investigator&#xD;
&#xD;
          7. Pregnant or lactating women&#xD;
&#xD;
          8. Sexually active women of childbearing potential not consistently and correctly&#xD;
             practicing birth control by implants, injectables, combined oral contraceptives,&#xD;
             hormonal intrauterine devices (IUDs), sexual abstinence or vasectomized partner&#xD;
&#xD;
          9. Lack of compliance or other similar reason that, according to investigator, precludes&#xD;
             satisfactory participation in the study&#xD;
&#xD;
             Target Disease Exclusions&#xD;
&#xD;
         10. History of Type 2 diabetes, maturity onset diabetes of young (MODY), pancreatic&#xD;
             surgery or chronic pancreatitis&#xD;
&#xD;
         11. Any use of oral hypoglycemic agents within 12 months prior to the screening visit&#xD;
&#xD;
         12. History of diabetes ketoacidosis (DKA) within 12 weeks prior to prior to the screening&#xD;
             visit&#xD;
&#xD;
         13. History of diabetes insipidus&#xD;
&#xD;
         14. History of hospital admission for glycemic control (either hyperglycemia or&#xD;
             hypoglycemia) within 3 months prior to prior to the screening visit&#xD;
&#xD;
         15. Frequent episodes of hypoglycemia as defined by more than one episode requiring&#xD;
             assistance, emergency care (paramedics or emergency room care) or glucagon therapy, or&#xD;
             more than 2 unexplained episodes of symptomatic hypoglycemia within 3 months prior to&#xD;
             the screening visit. An unexplained event is defined as an event that cannot be&#xD;
             explained by circumstances such as dietary (e.g. missed meal), strenuous exercise,&#xD;
             error in insulin dosing, etc.&#xD;
&#xD;
         16. Hypoglycemic unawareness&#xD;
&#xD;
         17. History of Addison's disease or chronic adrenal insufficiency&#xD;
&#xD;
             Physical and Laboratory Test Findings&#xD;
&#xD;
         18. Aspartate aminotransferase (AST) &gt; 2x Upper limit of normal (ULN)&#xD;
&#xD;
         19. Alanine aminotransferase (ALT) &gt; 2x ULN&#xD;
&#xD;
         20. Serum total bilirubin &gt; 2x ULN&#xD;
&#xD;
         21. Estimated GFR (eGFR) by the Modification of Diet in Renal Disease (MDRD) formula ≤ 60&#xD;
             ml/min/1.73m2. The renal function, eGFR will be estimated by the abbreviated MDRD,&#xD;
             using laboratory measurements of serum creatinine collected at screening [eGFR&#xD;
             (ml/min/1.73m2) = 175 x (standardized Scr)-1.154 x (Age)-0.203 x (0.742 if female) x&#xD;
             (1.212 if Black)].&#xD;
&#xD;
         22. Hemoglobin ≤ 11.0 g/dl (110 g/l) for boys / men; hemoglobin ≤10.0 g/dl (100 g/L) for&#xD;
             girls / women.&#xD;
&#xD;
         23. Creatine kinase (CK) &gt; 3x ULN&#xD;
&#xD;
         24. Positive for hepatitis B surface antigen or anti-hepatitis C virus antibody.&#xD;
&#xD;
         25. Abnormal Free T4 Note: abnormal TSH value at screening will be further evaluated for&#xD;
             free T4. Subjects with abnormal free T4 values will be excluded. A one-time retest may&#xD;
             be allowed, as determined by the Investigator, after a minimum of 6 weeks following&#xD;
             the adjustment of thyroid hormone replacement therapy in subject who have had a prior&#xD;
             diagnosis of a thyroid disorder and who are currently receiving thyroid replacement&#xD;
             therapy. Such cases should be discussed with the Investigator prior to retesting. The&#xD;
             subject must have all screening procedures and laboratory assessments performed as&#xD;
             part of this re-test, and all of these must meet enrolment eligibility criteria. The&#xD;
             subject's number will, however, remain the same as initially assigned.&#xD;
&#xD;
             Allergies and Adverse Drug Reaction&#xD;
&#xD;
         26. Allergies or contraindication to the contents of dapagliflozin tablets or insulin&#xD;
&#xD;
         27. Renal, Hepatic, Hematological/Oncological Diseases/Conditions&#xD;
&#xD;
         28. History of unstable or rapidly progressing renal disease&#xD;
&#xD;
         29. Conditions of congenital renal glucosuria&#xD;
&#xD;
         30. Renal allograft&#xD;
&#xD;
         31. Significant hepatic disease, including but not limited to, chronic active hepatitis&#xD;
             and/or severe hepatic insufficiency&#xD;
&#xD;
         32. Documented history of hepatotoxicity with any medication&#xD;
&#xD;
         33. Documented history of severe hepatobiliary disease&#xD;
&#xD;
         34. History of hemoglobinopathy, with the exception of sickle cell trait (SA) or&#xD;
&#xD;
         35. thalassemia minor; or chronic or recurrent hemolysis&#xD;
&#xD;
         36. Donation of blood or blood products to a blood bank, blood transfusion, or&#xD;
&#xD;
         37. participation in a clinical study requiring withdrawal of &gt; 400 mL of blood during the&#xD;
             6 weeks prior to the enrolment visit&#xD;
&#xD;
         38. Known immunocompromised status, including but not limited to, individuals who have&#xD;
&#xD;
         39. undergone organ transplantation or who are positive for the human immunodeficiency&#xD;
             virus&#xD;
&#xD;
         40. Malignancy within 5 years of the screening visit (with the exception of treated basal&#xD;
             cell or treated squamous cell carcinoma of the skin) Other Exclusion Criteria&#xD;
&#xD;
         41. Prisoners or subjects who are involuntarily incarcerated&#xD;
&#xD;
         42. Subjects who are compulsorily detained for treatment of either a psychiatric or&#xD;
             physical (eg, infectious disease) illness&#xD;
&#xD;
         43. Replacement or chronic systemic corticosteroid therapy, defined as any dose of&#xD;
             systemic corticosteroid taken for &gt; 4 weeks within 3 months prior to Day -3 visit.&#xD;
&#xD;
             NOTE: Topical or inhaled corticosteroids are allowed.&#xD;
&#xD;
         44. Any unstable endocrine, psychiatric, rheumatic disorders as judged by the&#xD;
             Investigator.&#xD;
&#xD;
         45. Subject is, in the judgment of the Investigator, unlikely to comply with the protocol&#xD;
             or has any severe concurrent medical or psychological condition that may affect the&#xD;
             interpretation of efficacy or safety data.&#xD;
&#xD;
         46. Subject with any condition which, in the judgment of the Investigator, may render the&#xD;
             subject unable to complete the study or which may pose a significant risk to the&#xD;
             subject.&#xD;
&#xD;
         47. Subject is currently abusing alcohol or other drugs or has done so within the last 6&#xD;
             months.&#xD;
&#xD;
         48. Subject is a participating investigator, study coordinator, employee of an&#xD;
             investigator or immediate family member of any of the aforementioned.&#xD;
&#xD;
         49. Administration of any other investigational drug within 30 days of planned enrolment&#xD;
             to this study.&#xD;
&#xD;
         50. No clinical conditions or clinically significant abnormalities, in any laboratory&#xD;
             value(s) collected after screening and prior to randomization which, in the&#xD;
             Investigator's judgment, should preclude entry into the treatment period.&#xD;
&#xD;
             Dosing day exclusion criteria&#xD;
&#xD;
         51. Subjects who meet one or more of the dosing day exclusion criteria will be excluded&#xD;
             from the dosing visit or withdrawn from the trial as specified below:&#xD;
&#xD;
         52. Non-fasting, ie, consumption of food or beverages other than water, later than at&#xD;
             23:00 hours the evening before dosing.&#xD;
&#xD;
         53. Clinically significant illness with onset within 4 weeks prior to dosing&#xD;
&#xD;
         54. Presence of clinically significant acute gastrointestinal symptoms (eg nausea,&#xD;
             vomiting, heartburn or diarrhoea), as judged by the investigator&#xD;
&#xD;
         55. Consumption of alcohol within 24 hours prior to dosing&#xD;
&#xD;
         56. Episode of severe hypoglycemia occurring within the last 24 hours prior to dosing&#xD;
&#xD;
         57. Any medical condition that, in the opinion of the Investigator, could interfere with&#xD;
             insulin pharmacokinetics and/or glucose metabolism.&#xD;
&#xD;
         58. Use of the following: systemic (oral or i.v.) corticosteroids, monoamine oxidase (MAO)&#xD;
             inhibitors, systemic non-selective beta-blockers, growth hormone, non-routine vitamins&#xD;
             or herbal products. Furthermore, thyroid hormones are not allowed unless the subject&#xD;
             has used stable medication during the past 3 months.&#xD;
&#xD;
         59. Non-adherence to pre-dosing insulin regimen consisting of CSII&#xD;
&#xD;
         60. Subjects who meet one or more of dosing day exclusion criteria will be excluded from&#xD;
             the dosing visit. In case a subject is excluded from the dosing visit, the dosing&#xD;
             visit can be rescheduled 1-7 days later. Each of the dosing visits can only be&#xD;
             rescheduled once.&#xD;
&#xD;
             -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>21 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Thomas Danne, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Kinder- und Jugendkrankenhaus AUF DER BULT</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Kinder - und Jugendkrankenhaus AUF DER BULT</name>
      <address>
        <city>Hannover</city>
        <zip>30173</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>February 2018</verification_date>
  <study_first_submitted>December 6, 2016</study_first_submitted>
  <study_first_submitted_qc>December 8, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 9, 2016</study_first_posted>
  <last_update_submitted>February 27, 2018</last_update_submitted>
  <last_update_submitted_qc>February 27, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">February 28, 2018</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>Diabetes Mellitus</mesh_term>
    <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>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT02987738
org study id: ESR-15-11453
nct id: NCT02987738
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Dapagliflozin has a unique mechanism of action that does not directly affect either insulin
      resistance or insulin secretion, but rather improves glycemia by reduction of glucose
      re-absorption from proximal renal tubules. Dapagliflozin is expected to reduce mean daily
      glucose, improve glycemic control and reduce overall insulin requirements. Improved glycemic
      control with reduced variability may also lead to reduced frequency of hypoglycemia.

      In youth with T1D, Dapagliflozin led to a significant reduction of insulin needed to achieve
      target glucose irrespective of preexisting HbA1c levels.

      In this pilot study data will be collected to investigate the effect on glucose of two doses
      of 10mg (each) dapagliflozin within range for the ensuing 24 hours during the DreaMed
      automated insulin delivery in patients with type 1 diabetes dosing with dapagliflozin in an
      in-patient setting combined with an automated sensor based CE marked insulin delivery system
      to data if dapagliflozin is a suitable add-on therapy. This will provide optimal monitoring
      of subject safety and assessment of the effects of dapagliflozin in a structured setting.

      If this inpatient study shows evidence that Dapagliflozin is a suitable add on therapy and
      leads to an increase of time within the target glucose range when using a sensor based
      insulin pump therapy (closed-loop) further outpatient studies are planned to be conducted.
The purpose of this pilot study is to collect clinical data of two doses of 10mg (each)
      dapagliflozin as add-on to night and day closed-loop control using the DreaMed automated
      insulin delivery on the time [%] within glucose range 70-180 mg/dl (3.9-10mmol/l) for the
      ensuing 24 hours with two oral mixed-meals.

      The study aimed to patients who have different degrees of inadequate glycemic control despite
      insulin use.

      A maximum of 45 patients will be screened until 30 Type 1 Diabetes mellitus patient (15
      adults, 15 adolescents) will completed the study.

      The trial will consist of six visits: a screening visit (Visit 1), two dosing visits (Visit 2
      and Visit 4), two phone visits (Visit 3 and Visit 5) and a follow-up visit (Visit 6).
      Furthermore, an information visit will take place prior to the screening visit in order to
      obtain patient's informed consent. Screening will take place 2-21 days prior to Visit 2 and
      the follow-up visit will take place 5-21 days after the end of Visit 4. The dosing visits
      will be separated by a wash-out period (5-30 days between the end of Visit 2 and begin of
      Visit 4) during which the subjects will resume their normal insulin treatment. Each phone
      visit (Visit 3 and Visit 5) will take place 3-5 days after the end of dosing Visits 2 and 4.
      The planned total duration of the trial is 18-78 days per subject (rescheduled visits
      excluded). Each subject will be randomised to a treatment sequence consisting of two
      treatment periods in which the subjects will receive 2 times 10mg dapagliflozin and placebo
      on two separate dosing visits.

      Subjects metabolic control will be achieved by using the DreaMed system (closed loop). The
      procedure will be used in order to aim and maintain blood glucose levels between 70 and 180
      mg/dl thereby.

      Two standardized mixed-meals will be given 12 hours and 18 hours after dosing. Blood glucose
      measurements will be performed every 30min for 120min after the mixed-meal.

      Blood samples for determination of dapagliflozin concentration in serum will be taken 14times
      in 24hours as well as ß-Hydroxybutyrate and every urine sample will be collected for 24 hours
      after first dosing for the determination of 24hour urinary glucose and creatinine for
      efficacy measurement.

      In addition a full blood gas analysis will be drawn if an elevated β-hydroxybutyrate of >1.0
      mmol/L will be detected.

      24 hours after first dosing with dapagliflozin/ placebo of each dosing visit the subjects
      will resume their usual insulin treatment and can leave the hospital.

      After conclusion of the trial the documented insulin doses over time will be summed up for
      calculation of the total insulin dose and the insulin dose per kg body weight per 24 hours.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Time in Range 70-180%
time frame: 24 hours
description: Collection of clinical data regarding the treatment of two doses of 10mg dapagliflozin as add-on to night and day closed-loop control using the DreaMed Algorithm and the time within glucose range 70-180 mg/dl (3.9-10mmol/l) [%]
measure: urinary glucose excretion
time frame: 24 hours
description: effect on urinary glucose excretion after a treatment with two doses of 10mg dapagliflozin (1x10 mg before bedtime and 1x10mg in the morning) in patients with type 1 diabetes
measure: postprandial insulin need
time frame: 24 hours
description: effect of postprandial insulin need after Treatment with dapagliflozin
measure: ß-hydroxybutyrate
time frame: 24 hours
description: association between Treatment of dapagliflozin and ß-hydroxybutyrate levels
measure: Reduction of Insulin dose
time frame: 24 hours
description: effect of insulin dose reduction during the DreaMed automated insulin delivery 24 hours after two doses of 10mg dapagliflozin in patients with type 1 diabetes
arm group label: dapagliflozin
arm group type: Experimental
description: two administrations of 10 mg dapagliflozin as tablet
arm group label: Placebo Oral Tablets
arm group type: Placebo Comparator
description: two administrations identical to the experimental drug
intervention type: Drug
intervention name: Dapagliflozin
description: two administrations in the evening and 12 hours later
arm group label: dapagliflozin
other name: Forxiga
intervention type: Drug
intervention name: Placebo Oral Tablet
description: two administrations in the evening and 12 hours later
arm group label: Placebo Oral Tablets
other name: Control
criteria: 
gender: All
minimum age: 12 Years
maximum age: 21 Years
healthy volunteers: No
last name: Thomas Danne, MD
role: Principal Investigator
affiliation: Kinder- und Jugendkrankenhaus AUF DER BULT
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 1
mesh term: Dapagliflozin
sharing ipd: No