NCT02987738

Pilot Study to Explore the Efficacy of DAPAglifozin as add-on to Closed-loop Control in Patients With Type 1 Diabetes

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)

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (actual)
• Sponsor: Kinderkrankenhaus auf der Bult · Academic / Other
• Sex: All
• Age: 12 Years – 21 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Type1diabetes

Interventions

Type	Name	Description
DRUG	Dapagliflozin	two administrations in the evening and 12 hours later
DRUG	Placebo Oral Tablet	two administrations in the evening and 12 hours later

Timeline

• Start date: 2017-02-09
• Primary completion: 2017-12-19
• Completion: 2017-12-19
• First posted: 2016-12-09
• Last updated: 2024-10-15

Locations

1 site across 1 country: Germany