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

Primary Purpose

Reperfusion Injury, Vascular Complications

Status

Recruiting

Phase

Phase 1

Locations

Austria

Study Type

Interventional

Intervention

Dapagliflozin 10mg

Placebo

About this trial

This is an interventional basic science trial for Reperfusion Injury focused on measuring dapagliflozin, forearm blood flow measurement, reperfusion injury, vascular function

Eligibility Criteria

18 Years - 40 Years (Adult)MaleAccepts Healthy Volunteers

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

Sites / Locations

Medical University of ViennaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Dapagliflozin

Dapagliflozin-placebo

Arm Description

14 day orally treatment with dapagliflozin

14 day orally treatment with dapagliflozin - placebo

Outcomes

Primary Outcome Measures

Acetylcholine - Area under the curve forearm blood flow measurement

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

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT05217654

First Posted

January 5, 2022

Last Updated

February 15, 2022

Sponsor

Medical University of Vienna

1. Study Identification

Unique Protocol Identification Number

NCT05217654

Brief Title

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

2. Study Status

Record Verification Date

February 2022

Overall Recruitment Status

Recruiting

Study Start Date

February 18, 2022 (Anticipated)

Primary Completion Date

February 1, 2023 (Anticipated)

Study Completion Date

August 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Medical University of Vienna

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Reperfusion Injury, Vascular Complications

Keywords

dapagliflozin, forearm blood flow measurement, reperfusion injury, vascular function

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

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.

Masking

ParticipantInvestigatorOutcomes Assessor

Masking Description

double-blind

Allocation

Randomized

Enrollment

32 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Dapagliflozin

Arm Type

Active Comparator

Arm Description

14 day orally treatment with dapagliflozin

Arm Title

Dapagliflozin-placebo

Arm Type

Placebo Comparator

Arm Description

14 day orally treatment with dapagliflozin - placebo

Intervention Type

Drug

Intervention Name(s)

Dapagliflozin 10mg

Other Intervention Name(s)

Forxiga 10mg Tabletten

Intervention Description

Daily orally administration of 10mg dapagliflozin

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

Placebo tablets

Intervention Description

Daily orally administration of 10mg dapagliflozin-placebo

Primary Outcome Measure Information:

Title

Acetylcholine - Area under the curve forearm blood flow measurement

Description

Time Frame

14 days

Title

Acetylcholine - Area under the curve forearm blood flow measurement

Description

Time Frame

30 min

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

40 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Martin Lutnik, M.D.

Phone

+43 1 40400

Ext

29810

martin.lutnik@meduniwien.ac.at

First Name & Middle Initial & Last Name or Official Title & Degree

Michael Wolzt, M.D.

Phone

+43 1 40400

Ext

29810

michael.wolzt@meduniwien.ac.at

Facility Information:

Facility Name

Medical University of Vienna

City

Vienna

ZIP/Postal Code

1090

Country

Austria

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Michael Wolzt, Prof. Dr.

Phone

+43 (0) 1 40400 29810

klin-pharmakologie@meduniwien.ac.at

First Name & Middle Initial & Last Name & Degree

Michael Wolzt, Prof. Dr.

First Name & Middle Initial & Last Name & Degree

Martin Lutnik, Dr.

First Name & Middle Initial & Last Name & Degree

Stefan Weisshaar, DDr.

12. IPD Sharing Statement

Plan to Share IPD

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

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