Dapagliflozin in Type 1 Diabetes

Study Overview
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Brief Summary
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Dapagliflozin is a highly selective, reversible and potent inhibitor of the sodium-glucose-linked Transporter 2 (SGLT2), which was successfully investigated for its use as a treatment option in type 2 diabetes mellitus. The effect of dapagliflozin is an increased glucosuria, and it was shown that mean blood glucose concentrations and postprandial glucose excursion in special were significantly reduced in type 2 diabetic patients. Due to its mechanism-of action it seems likely that also type 1 diabetic patients will benefit from dapagliflozin. The present study is focused on the effects of dapagliflozin on fasting glucose homeostasis and postprandial glucose excursion in male type 1diabetic patients. Participants will subsequently receive 10 milligrams of dapagliflozin and placebo for 3 days (equals 2 x 30mg per cross-over period) in a double-blind, randomised, cross-over design. The effects will be measured via euglycemic hyperinsulinemic clamp studies (fasting glucose homeostasis) and euglycemic oral glucose tolerance clamp tests (postprandial glucose excursions).

Official Title
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Short-term Effects of Dapagliflozin on Fasting and Postprandial Glucose Homeostasis in Male Type 1 Diabetes Patients.

Conditions
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Fasting Glucose, Glucose Excursion, Glycemic Control

Intervention / Treatment
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* Drug: Dapagliflozin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 1 diabetes mellitus (duration of disease at least 5 years) C-peptide concentration < 0.2µg/l male sex aged 18 to 60 years Body Mass Index 20 - 25 kg/m2 no measurable, clinically relevant ketonuria Exclusion Criteria: insufficient venous status on both forearms renal and/or hepatic insufficiency (including microalbuminuria and/or albumin/creatinin-ratio) history of cancer intake of medication and/or substances capable to influence insulin sensitivity within the last 3 months prior to study inclusion alcohol- and/or drug abuse, nicotine consumption > 5 cigarettes / 24h brittle-diabetes history of severe hypoglycemia, defined as the need for foreign assistance independent of actual blood glucose concentration measured history or evidence of any other clinically significant disorder, condition or disease other than those outlined above that, in the opinion of the investigator may compromise the ability of the participant to give written informed consent, would pose a risk to subject safety, or interfere with the study evaluation, procedures or completion.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: dapagliflozin<br>10mg dapagliflozin per 24h for 3 days per cross-over phase (equals 2 x 30mg) | Drug: Dapagliflozin<br>* euglycemic hyperinsulinemic clamp tests and euglycemic oral glucose tolerance clamp tests after the short-term (i.e.: 3 days, equals 10mg / 24h) intake of dapagliflozin<br>|
| Placebo Comparator: placebo sugar pills<br>placebo tablet, 1 per 24h for 3 days in total per cross-over phase (equals 2 x 3 tablets) | Drug: Dapagliflozin<br>* euglycemic hyperinsulinemic clamp tests and euglycemic oral glucose tolerance clamp tests after the short-term (i.e.: 3 days, equals 10mg / 24h) intake of dapagliflozin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| fasting glucose homeostasis | During hyperinsulinemic, euglycemic clamp studies, fasting glucose homeostasis will be determined for both, dapagliflozin and placebo. | study visit, immediatly | 
| postprandial glucose homeostasis | During euglycemic oral glucose tolerance clamp tests, postprandial glucose excursion will be determined and compared between dapagliflozin and placebo. | study visit, immediatly | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dapagliflozin, fasting glucose, postprandial glucose excursion, euglycemic hyperinsulinemic clamp, euglycemic oral glucose tolerance test