Reperfusion Injury, Vascular Complications
Conditions
Keywords
dapagliflozin, forearm blood flow measurement, reperfusion injury, vascular function
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.
Interventions
DRUGDapagliflozin 10mg
Daily orally administration of 10mg dapagliflozin
DRUGPlacebo
Daily orally administration of 10mg dapagliflozin-placebo
Sponsors
Medical University of Vienna
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
double-blind
Intervention model description
Prospective, randomized, placebo-controlled, double-blind, parallel group, phase 1 trial. Subjects in study group A will receive a daily oral dose of 10 mg dapagliflozin for 14 days (until study day 15) Subjects in study group B will receive a 14 day treatment with placebo-dapagliflozin.
Eligibility
Sex/Gender
MALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
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
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Acetylcholine - Area under the curve forearm blood flow measurement | 14 days | effect of dapagliflozin after a two weeks period of regular intake on forearm blood flow (FBF) reactivity in response to the vasodilators acetylcholine (ACh; endothelium-dependent agonist) or nitroglycerin (GTN; endothelium-independent vasodilator) |
Countries
Austria
Contacts
Primary ContactMartin Lutnik, M.D.
Backup ContactMichael Wolzt, M.D.
Outcome results
None listed