Study to Explore the Effect of Dapagliflozin and Stress in Adolescent and Adult Subjects With Type 1 Diabetes (T1D)

Sponsor
Kinderkrankenhaus auf der Bult
Study ID
NCT04234867
Phase
PHASE1
Status
Terminated

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 45 Years
Healthy Volunteers
Not accepted

Interventions

  • Dapagliflozin — DRUG
    once daily for 5 days
  • Placebo oral tablet — DRUG
    once daily for 5 days
  • Stress — OTHER
    single dose after last administration of experimental drug
  • Placebo Stress — OTHER
    single dose after last administration of experimental drug

Study Details

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.

Key Dates

Start date
May 18, 2022
Status verified
Dec 2024
Primary completion
Aug 26, 2022
Completion
Aug 26, 2022

Study Design

Enrollment
2 participants (actual)
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT

Arms

  • Experimental: Dapagliflozin - Stress
    Administration of 10mg dapagliflozin oral for 5 days and one i.v. administration of 250µg ACTH (Synacthen)
  • Experimental: Dapagliflozin and Placebo Stress
    Administration of 10mg dapagliflozin oral for 5 days and one i.v. administration of Placebo matching Synacthen
  • Placebo Comparator: Placebo Dapagliflozin and Stress
    Administration of placebo oral for 5 days identical to dapagliflozin and one i.v. administration of 250µg ACTH (Synacthen)
  • Placebo Comparator: Placebo Dapagliflozin and Placebo Stress
    Administration of placebo oral for 5 days identical to dapagliflozin and one i.v. administration of Placebo matching Synacthen

Primary Outcome Measure

time to development of DKA [ Time Frame: 12 hours ]

Related Studies