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This study is designed to investigate whether the sodium-glucose co-transporter-2 (SGLT-2) inhibitor Empagliflozin reduces sympathetic nervous system (SNS) activity in humans.
This is a randomised, double-blind, placebo controlled, cross-over study. Participants will be randomly assigned to receive either Empagliflozin 10mg/daily or Placebo and will later receive the alternate treatment.
Comprehensive testing will occur after each 4 week treatment phase and will include assessment of muscle sympathetic nerve activity, cardiac and renal noradrenaline spillover to assess organ specific SNS activity.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase 1 | Active Comparator | Empagliflozin 10mg daily or placebo |
|
| Phase2 | Placebo Comparator | Empagliflozin 10mg daily or placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Empagliflozin Oral Tablet [Jardiance] | Drug | Participants will be randomly assigned to receive either Empagliflozin 10mg/daily or Placebo and will later receive the alternate treatment. As the study is double blind neither the participant nor the study personnel will be aware of which treatment is currently being tested to avoid any effect this may have on the results. The two 4-week treatment phases will be separated by a 4-week wash out (drug-free) period. The study will consist of a total of 5 visits conducted over approximately 18 weeks; one screening visit, one baseline visit, 1 short visit at the start of the second treatment phase and 2 comprehensive testing visits, each at the end of the two treatment phases |
| Measure | Description | Time Frame |
|---|---|---|
| Reduction in cardiac sympathetic nerve activity | Cardiac sympathetic nerve activity assessed by cardiac noradrenaline spillover | 18 weeks |
| Reduction in renal sympathetic nerve activity | Renal sympathetic nerve activity assessed by renal noradrenaline spillover | 18 weeks |
| Reduction in muscle sympathetic nerve activity | Muscle sympathetic nerve activity assessed by microneurography | 18 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Reduction in ambulatory BP (blood pressure) | Blood Pressure assessed by ambulatory blood pressure monitoring | 18 weeks |
| Reduction in central Blood Pressure | central Blood Pressure assessed by Sphygmocor XCEL |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Anu Joyson, MSN | Contact | +61 8 92240390 | anu.joyson@uwa.edu.au |
| Name | Affiliation | Role |
|---|---|---|
| Markus Schlaich, MD,FAHA,FESC | Royal Perth Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Royal Perth Hospital | Recruiting | Perth | Western Australia | 6000 | Australia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26378978 | 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. | |
| 12948431 |
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Individual Participant Data will not be shared to maintain anonymity and confidentiality of the participants
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|
| Placebo Oral Tablet | Drug | Participants will be randomly assigned to receive either Empagliflozin 10mg/daily or Placebo and will later receive the alternate treatment. As the study is double blind neither the participant nor the study personnel will be aware of which treatment is currently being tested to avoid any effect this may have on the results. The two 4-week treatment phases will be separated by a 4-week wash out (drug-free) period. The study will consist of a total of 5 visits conducted over approximately 18 weeks; one screening visit, one baseline visit, 1 short visit at the start of the second treatment phase and 2 comprehensive testing visits, each at the end of the two treatment phases |
|
| 18 weeks |
| Change in urinary sodium excretion | Urinary sodium excretion assessed in a 24 hour urine sample | 18 weeks |
| Change in glycemic control | Glycemic control as assessed by an oral glucose tolerance test | 18 weeks |
| Hall JE, Jones DW, Kuo JJ, da Silva A, Tallam LS, Liu J. Impact of the obesity epidemic on hypertension and renal disease. Curr Hypertens Rep. 2003 Oct;5(5):386-92. doi: 10.1007/s11906-003-0084-z. |
| 17000932 | Background | Esler M, Straznicky N, Eikelis N, Masuo K, Lambert G, Lambert E. Mechanisms of sympathetic activation in obesity-related hypertension. Hypertension. 2006 Nov;48(5):787-96. doi: 10.1161/01.HYP.0000242642.42177.49. Epub 2006 Sep 25. No abstract available. |
| 23271752 | Background | Straznicky NE, Grima MT, Sari CI, Karapanagiotidis S, Wong C, Eikelis N, Richards KL, Lee G, Nestel PJ, Dixon JB, Lambert GW, Schlaich MP, Lambert EA. The relation of glucose metabolism to left ventricular mass and function and sympathetic nervous system activity in obese subjects with metabolic syndrome. J Clin Endocrinol Metab. 2013 Feb;98(2):E227-37. doi: 10.1210/jc.2012-3277. Epub 2012 Dec 27. |
| 23997009 | Background | Straznicky NE, Lambert EA, Grima MT, Eikelis N, Richards K, Nestel PJ, Dawood T, Masuo K, Sari CI, Dixon JB, Esler MD, Paul E, Schlaich MP, Lambert GW. The effects of dietary weight loss on indices of norepinephrine turnover: modulatory influence of hyperinsulinemia. Obesity (Silver Spring). 2014 Mar;22(3):652-62. doi: 10.1002/oby.20614. Epub 2013 Dec 6. |
| 12847071 | Background | Schlaich MP, Kaye DM, Lambert E, Sommerville M, Socratous F, Esler MD. Relation between cardiac sympathetic activity and hypertensive left ventricular hypertrophy. Circulation. 2003 Aug 5;108(5):560-5. doi: 10.1161/01.CIR.0000081775.72651.B6. Epub 2003 Jul 7. |
| 9562349 | Background | Ziegler D, Weise F, Langen KJ, Piolot R, Boy C, Hubinger A, Muller-Gartner HW, Gries FA. Effect of glycaemic control on myocardial sympathetic innervation assessed by [123I]metaiodobenzylguanidine scintigraphy: a 4-year prospective study in IDDM patients. Diabetologia. 1998 Apr;41(4):443-51. doi: 10.1007/s001250050928. |
| 20174639 | Background | Sverrisdottir YB, Jansson LM, Hagg U, Gan LM. Muscle sympathetic nerve activity is related to a surrogate marker of endothelial function in healthy individuals. PLoS One. 2010 Feb 17;5(2):e9257. doi: 10.1371/journal.pone.0009257. |
| 21518978 | Background | Mahfoud F, Schlaich M, Kindermann I, Ukena C, Cremers B, Brandt MC, Hoppe UC, Vonend O, Rump LC, Sobotka PA, Krum H, Esler M, Bohm M. Effect of renal sympathetic denervation on glucose metabolism in patients with resistant hypertension: a pilot study. Circulation. 2011 May 10;123(18):1940-6. doi: 10.1161/CIRCULATIONAHA.110.991869. Epub 2011 Apr 25. |
| ID | Term |
|---|---|
| D024821 | Metabolic Syndrome |
| D003924 | Diabetes Mellitus, Type 2 |
| D009765 | Obesity |
| ID | Term |
|---|---|
| D007333 | Insulin Resistance |
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D003920 | Diabetes Mellitus |
| D004700 | Endocrine System Diseases |
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C570240 | empagliflozin |
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