Trial to Investigate the Effect of Dapagliflozin on Ischemia Reperfusion Induced Endothelial Dysfunction

Phase 1

• Conditions: Reperfusion Injury; Vascular Complications
• Interventions: Drug: Dapagliflozin 10mg; Drug: Placebo

• Registration Number: NCT05217654
• Lead Sponsor: Medical University of Vienna

Brief Summary

The aim of the study is to investigate the effect of dapagliflozin or placebo on acetylcholine (Ach)- or nitroglycerin (GTN)-induced vasodilation of the forearm resistance vasculature, as determined by FBF measurement before and 10 minutes after 20 minutes of forearm ischemia.

Detailed Description

The aim is to test the effect of dapagliflozin or placebo on ACh-induced vasodilatation of the forearm resistance vasculature as assessed by FBF measurement before and 10 min after a 20 min forearm ischemia as well as after a 14 day treatment period. The area under the dose-effect curve (AUC) of different ACh doses will be calculated and compared between treatment groups (dapagliflozin vs. placebo) and different time points (pre-ischemia vs. post-ischemia). FBF measurements will be made in response to increasing intra-arterial doses of ACh (25, 50, 100 nmol/min) to assess endothelial function or GTN (4, 8, 16 nmol/min) to test vascular smooth muscle vasodilator function.

Study Timeline

• Study First Submitted: 2022-01-05
• Study First Submitted QC: 2022-01-20
• Status Verified: 2022-02
• Study First Posted: 2022-02-01
• Last Update Submitted: 2022-02-15
• Last Update Posted: 2022-02-16
• Study Start: 2022-02-18
• Primary Completion: 2023-02-01
• Study Completion: 2023-08-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Male
• Target Recruitment: 32

Inclusion Criteria

• Healthy male subjects; 18 - 40 years of age
• Body mass index between 18 and 27 kg/m2
• Written informed consent
• Normal findings in medical history
• Non-smoking

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Exclusion Criteria

• Regular intake of any medication including OTC drugs and herbals within 2 weeks before IMP administration
• History of occlusive vascular diseases
• History of vascular anomalies
• History of coagulation disorders
• History of diabetes mellitus (Type 1&2) or pre-diabetes (i.e. HbA1c ≥ 5,7 %)
• History of kidney disease
• History of ketoacidosis
• Impaired liver function (AST, ALT, gGT, bilirubin >3 x ULN)
• Impaired renal function (serum creatinine > 1.3 mg/dl)
• Any other relevant deviation from the normal range in clinical chemistry, haematology or urine analysis
• HIV-1/2-Ab, HbsAg or HCV-Ab positive serology
• Systolic blood pressure above 145 mmHg, diastolic blood pressure above 95 mmHg
• Known allergy against any test agent under study and/or lactose intolerance
• Regular daily consumption of more than on litre of xanthine-containing beverages or more than 40g alcohol
• Participation in another clinical trial during the preceding 3 weeks

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dapagliflozin	Dapagliflozin 10mg	14 day orally treatment with dapagliflozin
Dapagliflozin-placebo	Placebo	14 day orally treatment with dapagliflozin - placebo

Primary Outcome Measures

Name	Time	Method
Acetylcholine - Area under the curve forearm blood flow measurement	30 min	acute effect of dapagliflozin on forearm blood flow (FBF) reactivity in response to the vasodilators acetylcholine (ACh; endothelium-dependent agonist) or nitroglycerin (GTN; endothelium-independent vasodilator) 10 min before (baseline) and after 20 min forearm ischemia, respectively.

Trial Locations

Locations (1)

Medical University of Vienna; 🇦🇹 Vienna, Austria