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

Sponsor

Medical University of Vienna (Other)

Overall Status

Recruiting

CT.gov ID

NCT05217654

Collaborator

(none)

Enrollment

Location

Arms

17.4

Anticipated Duration (Months)

1.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Reperfusion Injury Vascular Complications	Drug: Dapagliflozin 10mg Drug: Placebo	Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

32 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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.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.

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Masking Description:

double-blind

Primary Purpose:

Basic Science

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

Anticipated Study Start Date :

Feb 18, 2022

Anticipated Primary Completion Date :

Feb 1, 2023

Anticipated Study Completion Date :

Aug 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Dapagliflozin 14 day orally treatment with dapagliflozin	Drug: Dapagliflozin 10mg Daily orally administration of 10mg dapagliflozin Other Names: Forxiga 10mg Tabletten
Placebo Comparator: Dapagliflozin-placebo 14 day orally treatment with dapagliflozin - placebo	Drug: Placebo Daily orally administration of 10mg dapagliflozin-placebo Other Names: Placebo tablets

Arm

Intervention/Treatment

Active Comparator: Dapagliflozin

14 day orally treatment with dapagliflozin

Drug: Dapagliflozin 10mg

Daily orally administration of 10mg dapagliflozin

Other Names:

Forxiga 10mg Tabletten

Placebo Comparator: Dapagliflozin-placebo

14 day orally treatment with dapagliflozin - placebo

Drug: Placebo

Daily orally administration of 10mg dapagliflozin-placebo

Other Names:

Placebo tablets

Outcome Measures

Primary Outcome Measures

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)
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 40 Years

Sexes Eligible for Study:

Male

Accepts 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