Role of Canagliflozin on CD34+ Cells in Patients With Type 2 Diabetes

Summary

The investigators hypothesize that Cana may be able to improve number and function of CD34+ endothelial progenitor cells. The investigators also propose that this expected cardiovascular benefit is independent of HbA1C reduction. Subjects will begin taking 100 mg of Cana or placebo after initial 4 weeks. Subjects will be withdrawn from the study if the medication or placebo is not tolerated.

Timeline

Start

2016-11

Primary completion

2020-01

Completion

2020-09

Publications

• Background Sen S, Strappe PM, O'Brien T. Gene transfer in endothelial dysfunction and hypertension. Methods Mol Med. 2005;108:299-314. doi: 10.1385/1-59259-850-1:299.
• Background Krenning G, Dankers PY, Drouven JW, Waanders F, Franssen CF, van Luyn MJ, Harmsen MC, Popa ER. Endothelial progenitor cell dysfunction in patients with progressive chronic kidney disease. Am J Physiol Renal Physiol. 2009 Jun;296(6):F1314-22. doi: 10.1152/ajprenal.90755.2008. Epub 2009 Apr 1.
• Background Department of Health and Human Services, NIH and National Center for Chronic Disease Prevention and Health Promotion, "National Diabetes Statistics: 2007 and 2011 Fact Sheet." 2011
• Background American Diabetes Association. Standards of medical care in diabetes--2014. Diabetes Care. 2014 Jan;37 Suppl 1:S14-80. doi: 10.2337/dc14-S014. No abstract available.
• Background Afkarian M, Sachs MC, Kestenbaum B, Hirsch IB, Tuttle KR, Himmelfarb J, de Boer IH. Kidney disease and increased mortality risk in type 2 diabetes. J Am Soc Nephrol. 2013 Feb;24(2):302-8. doi: 10.1681/ASN.2012070718. Epub 2013 Jan 29.
• Background Rask-Madsen C, King GL. Mechanisms of Disease: endothelial dysfunction in insulin resistance and diabetes. Nat Clin Pract Endocrinol Metab. 2007 Jan;3(1):46-56. doi: 10.1038/ncpendmet0366.
• Background Stanton RC. Sodium glucose transport 2 (SGLT2) inhibition decreases glomerular hyperfiltration: is there a role for SGLT2 inhibitors in diabetic kidney disease? Circulation. 2014 Feb 4;129(5):542-4. doi: 10.1161/CIRCULATIONAHA.113.007071. Epub 2013 Dec 13. No abstract available.
• Background Oliva RV, Bakris GL. Blood pressure effects of sodium-glucose co-transport 2 (SGLT2) inhibitors. J Am Soc Hypertens. 2014 May;8(5):330-9. doi: 10.1016/j.jash.2014.02.003. Epub 2014 Feb 12.
• Background Sabyasachi Sen, Sarah Witkowski, Ann Lagoy, Ashequl M. Islam: A six-week home exercise program improves endothelial function and CD34+ circulating progenitor cells in patients with pre-diabetes. J Endocrinol Metab.2015; 5 (1-2):163-171, doi: http://dx.doi.org/10.14740/jem273w.
• Background Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A, Bohm M, Nickenig G. Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med. 2005 Sep 8;353(10):999-1007. doi: 10.1056/NEJMoa043814.
• Background Losordo DW, Schatz RA, White CJ, Udelson JE, Veereshwarayya V, Durgin M, Poh KK, Weinstein R, Kearney M, Chaudhry M, Burg A, Eaton L, Heyd L, Thorne T, Shturman L, Hoffmeister P, Story K, Zak V, Dowling D, Traverse JH, Olson RE, Flanagan J, Sodano D, Murayama T, Kawamoto A, Kusano KF, Wollins J, Welt F, Shah P, Soukas P, Asahara T, Henry TD. Intramyocardial transplantation of autologous CD34+ stem cells for intractable angina: a phase I/IIa double-blind, randomized controlled trial. Circulation. 2007 Jun 26;115(25):3165-72. doi: 10.1161/CIRCULATIONAHA.106.687376. Epub 2007 Jun 11.
• Background Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE; EMPA-REG OUTCOME Investigators. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015 Nov 26;373(22):2117-28. doi: 10.1056/NEJMoa1504720. Epub 2015 Sep 17.
• Results Nandula SR, Kundu N, Awal HB, Brichacek B, Fakhri M, Aimalla N, Elzarki A, Amdur RL, Sen S. Role of Canagliflozin on function of CD34+ve endothelial progenitor cells (EPC) in patients with type 2 diabetes. Cardiovasc Diabetol. 2021 Feb 13;20(1):44. doi: 10.1186/s12933-021-01235-4.

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