Clinical trial NCT05217654: Trial to Investigate the Effect of Dapagliflozin on Ischemia Reperfusion Induced Endothelial Dysfunction
Official title: A Randomized, Double - Blind, Placebo - Controlled Trial to Investigate the Effect of Dapagliflozin on Ischemia Reperfusion Induced Endothelial Dysfunction of the Forearm Vasculature in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Reperfusion Injury
Vascular Complications
Keywords: dapagliflozin
forearm blood flow measurement
reperfusion injury
vascular function
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
First posted: 2022-02-01
Enrollment: 32
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Acetylcholine - Area under the curve forearm blood flow measurement
timeFrame: 14 days
measure: Acetylcholine - Area under the curve forearm blood flow measurement
timeFrame: 30 min
Secondary outcomes:
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna
Study officials:
References:
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