Pilot Study to Explore the Efficacy of DAPAglifozin as add-on to Closed-loop Control in Patients With Type 1 Diabetes
Condition: Type1diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Dapagliflozin; Placebo Oral Tablet
Intervention type(s): Drug; Drug
Intervention description(s): two administrations in the evening and 12 hours later; two administrations in the evening and 12 hours later
Other intervention name(s): Forxiga; Control
Intervention MeSH terms: Dapagliflozin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment