NCT04234867: Dapa-Stress

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

Terminated Phase 1 Last updated 9 December 2024

What this trial tests

Phase 1 trial testing Dapagliflozin in Type 1 Diabetes in 2 participants. Terminated before completion.

Timeline

18 May 2022

Primary endpoint
26 August 2022

26 August 2022

Quick facts

Lead sponsor	Kinderkrankenhaus auf der Bult
Phase	Phase 1
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	triple
Primary purpose	treatment
Enrollment	2
Start date	18 May 2022
Primary completion	26 August 2022
Estimated completion	26 August 2022
Sites	1 location across Germany

Drugs / interventions tested

• Dapagliflozin (DAPAGLIFLOZIN) — full drug profile →
• Placebo oral tablet — full drug profile →
• Stress — full drug profile →
• Placebo Stress

Conditions studied

• Type 1 Diabetes — all drugs for Type 1 Diabetes →
• Diabetic Ketoacidosis — all drugs for Diabetic Ketoacidosis →

Sponsor

Kinderkrankenhaus auf der Bult — full company profile →

Who can join

Adults 18 to 45, any sex, with Type 1 Diabetes or Diabetic Ketoacidosis. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. SGLT2 Inhibitors in the Management of Type 1 Diabetes (T1D): An Update on Current Evidence and Recommendations.
   Maffei P, Bettini S, Busetto L, Dassie F. · · 2023 · cited 31× · PMID 37964939 · DOI 10.2147/dmso.s240903