Effects of Dapagliflozin on Central Hemodynamics and Urine Albumin Excretion in Patients With Type 2 Diabetes.

Summary

This study is designed to test the hypothesis that the treatment-induced reductions in the ambulatory aortic pressure are more pronounced in the group of dapagliflozin than in the group of placebo. It is a 12 week, double-blind, randomized, placebo-controlled clinical trial of dapagliflozin versus placebo in 160 adult patients with type 2 diabetes mellitus (DM). It will be conducted in three centers. Potentially eligible patients will be asked to provide written informed consent (Screening Visit). Patients, who fulfill the inclusion and exclusion criteria, will be asked to visit the sites one week (Visit 1 - V1) after the screening visit. On Visit 2 (V2) all eligible patients will be randomized to one of the two treatment arms and will continue with the next visits as appropriate (Visit 3, Telephone Visit 1, Visit 4-end of study). Aortic blood pressure (BP) and arterial stiffness parameters will be measured as indicated by the protocol in V1 and V3 with the Mobil-O-Graph monitor. Blood samples will be collected as indicated by the protocol in Screening Visit for the measurement of glycated hemoglobin (HbA1c), creatinine and liver function parameters. In addition, blood samples will be collected in V1 and V3 for routine hematological and biochemical tests including creatinine, fasting glucose, HbA1c, lipid profile and liver function parameters. Urine samples will be collected as indicated by the protocol in V1 and V3 for the measurement of albumin to creatinine ratio.

Timeline

Start

2016-10

Primary completion

2019-06

Completion

2019-10

Publications

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• Background Tziomalos K, Athyros VG, Karagiannis A. Treating Arterial Stiffness in Young and Elderly Patients with the Metabolic Syndrome. Curr Pharm Des. 2014;20(39):6106-13. doi: 10.2174/1381612820666140417101523.
• Background Jankowski P, Kawecka-Jaszcz K, Czarnecka D, Brzozowska-Kiszka M, Styczkiewicz K, Loster M, Kloch-Badelek M, Wilinski J, Curylo AM, Dudek D; Aortic Blood Pressure and Survival Study Group. Pulsatile but not steady component of blood pressure predicts cardiovascular events in coronary patients. Hypertension. 2008 Apr;51(4):848-55. doi: 10.1161/HYPERTENSIONAHA.107.101725. Epub 2008 Feb 11.
• Background Katsiki N, Koumaras C, Athyros VG, Karagiannis A. Thinking beyond traditional cardiovascular risk factors: the role of arterial stiffness in targeting residual risk. Angiology. 2012 Jan;63(1):9-11. doi: 10.1177/0003319711406256. No abstract available.
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• Background Protogerou AD, Argyris A, Nasothimiou E, Vrachatis D, Papaioannou TG, Tzamouranis D, Blacher J, Safar ME, Sfikakis P, Stergiou GS. Feasibility and reproducibility of noninvasive 24-h ambulatory aortic blood pressure monitoring with a brachial cuff-based oscillometric device. Am J Hypertens. 2012 Aug;25(8):876-82. doi: 10.1038/ajh.2012.63. Epub 2012 Jun 7.
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• Background Weber T, Wassertheurer S, Rammer M, Maurer E, Hametner B, Mayer CC, Kropf J, Eber B. Validation of a brachial cuff-based method for estimating central systolic blood pressure. Hypertension. 2011 Nov;58(5):825-32. doi: 10.1161/HYPERTENSIONAHA.111.176313. Epub 2011 Sep 12.
• Background Papaioannou TG, Argyris A, Protogerou AD, Vrachatis D, Nasothimiou EG, Sfikakis PP, Stergiou GS, Stefanadis CI. Non-invasive 24 hour ambulatory monitoring of aortic wave reflection and arterial stiffness by a novel oscillometric device: the first feasibility and reproducibility study. Int J Cardiol. 2013 Oct 25;169(1):57-61. doi: 10.1016/j.ijcard.2013.08.079. Epub 2013 Sep 8.
• Background Franssen PM, Imholz BP. Evaluation of the Mobil-O-Graph new generation ABPM device using the ESH criteria. Blood Press Monit. 2010 Aug;15(4):229-31. doi: 10.1097/mbp.0b013e328339be38.
• Background Wei W, Tolle M, Zidek W, van der Giet M. Validation of the mobil-O-Graph: 24 h-blood pressure measurement device. Blood Press Monit. 2010 Aug;15(4):225-8. doi: 10.1097/MBP.0b013e328338892f.
• Background Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, Pannier B, Vlachopoulos C, Wilkinson I, Struijker-Boudier H; European Network for Non-invasive Investigation of Large Arteries. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J. 2006 Nov;27(21):2588-605. doi: 10.1093/eurheartj/ehl254. Epub 2006 Sep 25.
• Background Hametner B, Wassertheurer S, Kropf J, Mayer C, Eber B, Weber T. Oscillometric estimation of aortic pulse wave velocity: comparison with intra-aortic catheter measurements. Blood Press Monit. 2013 Jun;18(3):173-6. doi: 10.1097/MBP.0b013e3283614168.
• Background Protogerou AD, Smulyan H, Safar ME. Closer to noninvasive out-of-office aortic blood pressure assessment: a time to think and act. Hypertension. 2011 Nov;58(5):765-7. doi: 10.1161/HYPERTENSIONAHA.111.177501. Epub 2011 Sep 12. No abstract available.
• Papadopoulou E, Theodorakopoulou MP, Loutradis C, Tzanis G, Tzatzagou G, Kotsa K, Zografou I, Tsapas A, Karagiannis A, Sarafidis P. Dapagliflozin Does Not Affect Short-Term Blood Pressure Variability in Patients With Type 2 Diabetes Mellitus. Am J Hypertens. 2021 Apr 20;34(4):404-413. doi: 10.1093/ajh/hpaa207.

Drugs

Indications