Study to Explore the Effect of Dapagliflozin and Stress in Adolescent and Adult Subjects With Typ… (NCT04234867) | Clinical Trial Compass
TerminatedPhase 1
Study to Explore the Effect of Dapagliflozin and Stress in Adolescent and Adult Subjects With Type 1 Diabetes (T1D)
Stopped: slow recruitment
Germany2 participantsStarted 2022-05-18
Plain-language summary
Type 1 Diabetes is characterized by an absolute lack of insulin caused by autoimmune ß-cell destruction. Looking for different therapeutic approaches, beyond the administration of Insulin SGLT-Inhibitors (SGLT=sodium-glucose cotransporter) like Dapagliflozin look like a promising option to avoid hyperglycaemic excursions which are a reason for glycaemic variability by renal excretion of excessive glucose without administration of extra insulin. But also euglycemic DKA has been reported during SGLT2 add-on therapy to insulin in T1D and mechanistic studies have been called for.
The role of Dapagliflozin-induced hyperglucagonemia and stress/infection precipitating euglycemic DKA in this situation is unclear.
Thus the purpose of this pilot study is to collect clinical data on the development of DKA after insulin-withdrawal with Dapagliflozin compared to placebo and the added effect of a single dose of 4mg/kg i.v. ACTH as mediator of stress.
The first objective is to investigate the time to DKA (defined as Bicarbonate \<19 mmol/l) after insulin withdrawal during treatment with a stable 5 day single daily dose of 10mg Dapagliflozin in patients with type 1 Diabetes.
In addition it should be evaluate the additional effect of stress, modelled by a single injection of ACTH on DKA development during Dapagliflozin Treatment.
We also want to know if Dapagliflozin influences glucagon levels during insulin withdrawal and how this is associated with the time course of DKA development.
Who can participate
Age range18 Years – 45 Years
SexALL
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Inclusion criteria
✓. Provision of informed consent from participant and all legal representatives prior to any study specific procedures
✓. Age: Female and/or male aged \>18 years
✓. Subject must have type 1 diabetes (as diagnosed clinically) ≥ 12 months
✓. HbA1c \<10 %
✓. Insulin use with an average daily dose between 0.6 - 2.0 U/kg administered by insulin pump (CSII)
✓. BMI 23.0 to 35.0 kg/m2 minimum weight of 50 kg
✓. Women of childbearing potential (WOCBP) must be using an acceptable method of contraception to avoid pregnancy throughout the study as judged by the investigator
✓. WOCBP must have a negative serum pregnancy test at screening as well as negative urine tests at follow up visits
. History of T2DM (type 2 diabetes mellitus), maturity onset diabetes of young (MODY), pancreatic surgery or chronic pancreatitis
✕. Any use of oral hypoglycemic agents within 2 weeks prior to the screening visit
✕. History of diabetes ketoacidosis (DKA) within 12 weeks prior to prior to the screening visit
✕. History of diabetes insipidus
✕. History of hospital admission for glycemic control (either hyperglycemia or hypoglycemia) within 3 months prior to prior to the screening visit
✕. Frequent episodes of hypoglycemia as defined by more than one episode requiring assistance, emergency care (paramedics or emergency room care) or glucagon therapy (in children defined as seizure or loss of consciousness) , or more than 2 unexplained episodes of symptomatic hypoglycemia within 3 months prior to the screening visit.