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

NCT05217654 | Unknown Phase 1

• 1 other identifier: FBF-SGLT2
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Reperfusion Injury; Vascular Complications

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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)

  14 days

• 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.

  30 min

Study Arms (2)

Dapagliflozin

ACTIVE COMPARATOR

14 day orally treatment with dapagliflozin

Drug: Dapagliflozin 10mg

Dapagliflozin-placebo

PLACEBO COMPARATOR

14 day orally treatment with dapagliflozin - placebo

Drug: Placebo

Interventions

Dapagliflozin 10mg DRUG

Daily orally administration of 10mg dapagliflozin

Also known as: Forxiga 10mg Tabletten

Dapagliflozin

Placebo DRUG

Daily orally administration of 10mg dapagliflozin-placebo

Also known as: Placebo tablets

Dapagliflozin-placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Medical University of Vienna

Vienna, 1090, Austria

RECRUITING

Related Publications (18)

• Eltzschig HK, Eckle T. Ischemia and reperfusion--from mechanism to translation. Nat Med. 2011 Nov 7;17(11):1391-401. doi: 10.1038/nm.2507.

  PMID: 22064429 BACKGROUND

• Szabo C. The pathophysiological role of peroxynitrite in shock, inflammation, and ischemia-reperfusion injury. Shock. 1996 Aug;6(2):79-88. doi: 10.1097/00024382-199608000-00001.

  PMID: 8856840 BACKGROUND

• Pleiner J, Schaller G, Mittermayer F, Marsik C, MacAllister RJ, Kapiotis S, Ziegler S, Ferlitsch A, Wolzt M. Intra-arterial vitamin C prevents endothelial dysfunction caused by ischemia-reperfusion. Atherosclerosis. 2008 Mar;197(1):383-91. doi: 10.1016/j.atherosclerosis.2007.06.011. Epub 2007 Jul 23.

  PMID: 17645881 BACKGROUND

• Lu Q, Liu J, Li X, Sun X, Zhang J, Ren D, Tong N, Li J. Empagliflozin attenuates ischemia and reperfusion injury through LKB1/AMPK signaling pathway. Mol Cell Endocrinol. 2020 Feb 5;501:110642. doi: 10.1016/j.mce.2019.110642. Epub 2019 Nov 21.

  PMID: 31759100 BACKGROUND

• Korkmaz-Icoz S, Kocer C, Sayour AA, Kraft P, Benker MI, Abulizi S, Georgevici AI, Brlecic P, Radovits T, Loganathan S, Karck M, Szabo G. The Sodium-Glucose Cotransporter-2 Inhibitor Canagliflozin Alleviates Endothelial Dysfunction Following In Vitro Vascular Ischemia/Reperfusion Injury in Rats. Int J Mol Sci. 2021 Jul 21;22(15):7774. doi: 10.3390/ijms22157774.

  PMID: 34360539 BACKGROUND

• Khemais-Benkhiat S, Belcastro E, Idris-Khodja N, Park SH, Amoura L, Abbas M, Auger C, Kessler L, Mayoux E, Toti F, Schini-Kerth VB. Angiotensin II-induced redox-sensitive SGLT1 and 2 expression promotes high glucose-induced endothelial cell senescence. J Cell Mol Med. 2020 Feb;24(3):2109-2122. doi: 10.1111/jcmm.14233. Epub 2019 Mar 30.

  PMID: 30929316 BACKGROUND

• Tsai KL, Hsieh PL, Chou WC, Cheng HC, Huang YT, Chan SH. Dapagliflozin attenuates hypoxia/reoxygenation-caused cardiac dysfunction and oxidative damage through modulation of AMPK. Cell Biosci. 2021 Feb 26;11(1):44. doi: 10.1186/s13578-021-00547-y.

  PMID: 33637129 BACKGROUND

• He C, Zhu H, Li H, Zou MH, Xie Z. Dissociation of Bcl-2-Beclin1 complex by activated AMPK enhances cardiac autophagy and protects against cardiomyocyte apoptosis in diabetes. Diabetes. 2013 Apr;62(4):1270-81. doi: 10.2337/db12-0533. Epub 2012 Dec 7.

  PMID: 23223177 BACKGROUND

• Chen X, Li X, Zhang W, He J, Xu B, Lei B, Wang Z, Cates C, Rousselle T, Li J. Activation of AMPK inhibits inflammatory response during hypoxia and reoxygenation through modulating JNK-mediated NF-kappaB pathway. Metabolism. 2018 Jun;83:256-270. doi: 10.1016/j.metabol.2018.03.004. Epub 2018 Mar 9.

  PMID: 29526538 BACKGROUND

• Liem DA, Verdouw PD, Duncker DJ. Transient limb ischemia induces remote ischemic preconditioning in vivo. Circulation. 2003 Jun 24;107(24):e218-9; author reply e218-9. doi: 10.1161/01.CIR.0000077520.36997.F9. No abstract available.

  PMID: 12821595 BACKGROUND

• Kharbanda RK, Peters M, Walton B, Kattenhorn M, Mullen M, Klein N, Vallance P, Deanfield J, MacAllister R. Ischemic preconditioning prevents endothelial injury and systemic neutrophil activation during ischemia-reperfusion in humans in vivo. Circulation. 2001 Mar 27;103(12):1624-30. doi: 10.1161/01.cir.103.12.1624.

  PMID: 11273988 BACKGROUND

• Benjamin N, Calver A, Collier J, Robinson B, Vallance P, Webb D. Measuring forearm blood flow and interpreting the responses to drugs and mediators. Hypertension. 1995 May;25(5):918-23. doi: 10.1161/01.hyp.25.5.918.

  PMID: 7737727 BACKGROUND

• Barcroft H, Edholm OG. The effect of temperature on blood flow and deep temperature in the human forearm. J Physiol. 1943 Jun 30;102(1):5-20. doi: 10.1113/jphysiol.1943.sp004009. No abstract available.

  PMID: 16991588 BACKGROUND

• Seman L, Macha S, Nehmiz G, Simons G, Ren B, Pinnetti S, Woerle HJ, Dugi K. Empagliflozin (BI 10773), a Potent and Selective SGLT2 Inhibitor, Induces Dose-Dependent Glucosuria in Healthy Subjects. Clin Pharmacol Drug Dev. 2013 Apr;2(2):152-61. doi: 10.1002/cpdd.16. Epub 2013 Mar 27.

  PMID: 27121669 BACKGROUND

• Fralick M, Schneeweiss S, Patorno E. Risk of Diabetic Ketoacidosis after Initiation of an SGLT2 Inhibitor. N Engl J Med. 2017 Jun 8;376(23):2300-2302. doi: 10.1056/NEJMc1701990. No abstract available.

  PMID: 28591538 BACKGROUND

• Weisshaar S, Litschauer B, Kerbel T, Wolzt M. Atorvastatin combined with ticagrelor prevent ischemia-reperfusion induced vascular endothelial dysfunction in healthy young males - A randomized, placebo-controlled, double-blinded study. Int J Cardiol. 2018 Mar 15;255:1-7. doi: 10.1016/j.ijcard.2017.12.067. Epub 2017 Dec 24.

  PMID: 29288055 BACKGROUND

• Weisshaar S, Litschauer B, Eipeldauer M, Hobl EL, Wolzt M. Ticagrelor mitigates ischaemia-reperfusion induced vascular endothelial dysfunction in healthy young males - a randomized, single-blinded study. Br J Clin Pharmacol. 2017 Dec;83(12):2651-2660. doi: 10.1111/bcp.13378. Epub 2017 Aug 22.

  PMID: 28715608 BACKGROUND

• Lutnik M, Weisshaar S, Litschauer B, Bayerle-Eder M, Niederdockl J, Wolzt M. Dapagliflozin prevents vascular ischemia-reperfusion injury in healthy young males: a randomized, placebo-controlled, double-blinded trial. Sci Rep. 2025 May 13;15(1):16633. doi: 10.1038/s41598-025-01405-4.

  PMID: 40360700 DERIVED

MeSH Terms

Conditions

Reperfusion Injury

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Martin Lutnik, M.D.

CONTACT

+43 1 40400; martin.lutnik@meduniwien.ac.at

Michael Wolzt, M.D.

CONTACT

+43 1 40400; michael.wolzt@meduniwien.ac.at

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: double-blind
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Univ. Prof. Dr.

Model Details: 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.

Study Record Dates

• First Submitted: January 5, 2022
• First Posted: February 1, 2022
• Study Start: February 18, 2022
• Primary Completion: February 1, 2023
• Study Completion: August 1, 2023
• Last Updated: February 16, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)