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

NCT ID: NCT05217654

Last Updated: 2022-02-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1

Total Enrollment

32 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-02-18

Study Completion Date

2023-08-01

Brief Summary

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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

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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.

Conditions

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Reperfusion Injury Vascular Complications

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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 Study Purpose

BASIC_SCIENCE

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors
double-blind

Study Groups

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Dapagliflozin

14 day orally treatment with dapagliflozin

Group Type ACTIVE_COMPARATOR

Dapagliflozin 10mg

Intervention Type DRUG

Daily orally administration of 10mg dapagliflozin

Dapagliflozin-placebo

14 day orally treatment with dapagliflozin - placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Daily orally administration of 10mg dapagliflozin-placebo

Interventions

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Dapagliflozin 10mg

Daily orally administration of 10mg dapagliflozin

Intervention Type DRUG

Placebo

Daily orally administration of 10mg dapagliflozin-placebo

Intervention Type DRUG

Other Intervention Names

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Forxiga 10mg Tabletten Placebo tablets

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

40 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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Medical University of Vienna

OTHER

Sponsor Role lead

Responsible Party

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Michael Wolzt, Prof. MD

Univ. Prof. Dr.

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Medical University of Vienna

Vienna, , Austria

Site Status RECRUITING

Countries

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Austria

Central Contacts

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Martin Lutnik, M.D.

Role: CONTACT

+43 1 40400 ext. 29810

Michael Wolzt, M.D.

Role: CONTACT

+43 1 40400 ext. 29810

Facility Contacts

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Michael Wolzt, Prof. Dr.

Role: primary

+43 (0) 1 40400 29810

References

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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.

Reference Type BACKGROUND
PMID: 22064429 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8856840 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17645881 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31759100 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 34360539 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30929316 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33637129 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23223177 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29526538 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12821595 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11273988 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7737727 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16991588 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27121669 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28591538 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29288055 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28715608 (View on PubMed)

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.

Reference Type DERIVED
PMID: 40360700 (View on PubMed)

Other Identifiers

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FBF-SGLT2

Identifier Type: -

Identifier Source: org_study_id

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