A placebo-controlled, randomized, double-blind trial to investigate the impact of dapagliflozin on the development of diabetic ketoacidosis and intermediate metabolism in type 1 diabetes using a dual stable tracer method: A safety study investigating the fuel shift theory in the human model

Phase 1

• Conditions: E10; Type 1 diabetes mellitus

• Registration Number: DRKS00021284
• Lead Sponsor: Medizinische Universität Graz, Universitätsklinik für Innere Medizin, Abteilung für Endokrinologie und Diabetologie

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-04-08
• Study Completion: 2020-09-28
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Complete
• Sex: Male
• Target Recruitment: 17

Inclusion Criteria

Men aged 18-55 years (both inclusive) at the time of signing the consent form
Diagnosis of type 1 diabetes mellitus.
C-peptide (fasting value) = 0.07 ng/ml (= 0.02 nmol/L).
Stable insulin therapy for at least 6 months prior to screening by continuous subcutaneous insulin infusion (CSII).
Body Mass Index (BMI) between 20.0 and 35.0 kg/m2 (both inclusive)
HbA1c = 85,8 mmol/mol (= 10,0 %).

Exclusion Criteria

People with muscular symptoms of hyperglycemia (tingling, pain). Known or suspected hypersensitivity to experimental products or other related products. History of severe allergy to medicines or foods or a history of severe anaphylactic reactions.
Presence of clinically relevant respiratory, cardiovascular, endocrine (except those related to diabetes mellitus), severe liver dysfunction, or other conditions that the investigator deems could compromise safety or compliance with the protocol. Receipt of an investigational medicinal product (IMP) within one month (or 5 half-life periods, whichever is longer) prior to screening. Uncontrolled hypertension is defined as blood pressure at screening (after 5 min rest) outside the range 90-160 mmHg for systolic or 50-100 mmHg for diastolic. Acute symptomatic (according to the investigator's assessment) urinary tract or genital infection, chronic or recurrent (= 3-year episodes) cystitis. Proliferative retinopathy or maculopathy (requiring treatment) and/or severe neuropathy, especially autonomic neuropathy, as determined by the investigator. Use of medications that may interfere with the interpretation of study results or are known to cause clinically relevant disturbances in insulin action, glucose utilization, or recovery from hypoglycemia (in the investigator's judgment). Hemoglobin < 12.5 g/dl, serum creatinine level = 1.43 mg/dl (= 126 µmol/L) (male), alanine transaminase (ALT) or alkaline phosphatase (ALP) > 2.5 x ULN. Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m². Positive laboratory result for screening test for HIV, hepatitis B and/or hepatitis C. Surgery or trauma with significant blood loss (more than 500 mL) within the last 3 months before screening. Smoker (defined as a subject who smokes at least five cigarettes or the equivalent product per day) who is unable or unwilling to refrain from smoking or from using nicotine gum or transdermal nicotine patches during the inpatient period Known or suspected alcohol or drug/chemical abuse (as determined by the investigator) or positive result of an alcohol test or positive result of a drug abuse test.

Study & Design

• Study Type: interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To compare the kinetics of DKA development in T1D patients treated with dapagliflozin vs. placebo in an insulin depletion experiment by monitoring bicarbonate.

Secondary Outcome Measures

Name	Time	Method
The secondary objective of this trial is to assess the differential effects of dapagliflozin 10 mg treatment compared to placebo on DKA-relevant parameters during an insulin depletion experiment.