EMPA-SNS: Effects of Sodium-glucose Co-transporter-2( SGLT-2 ) Inhibition on Sympathetic Nervous System Activity in Humans
Study Details
Study Description
Brief Summary
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
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Phase 4 |
Detailed Description
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Active Comparator: Phase 1 Empagliflozin 10mg daily or placebo |
Drug: Empagliflozin Oral Tablet [Jardiance]
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
Drug: Placebo Oral Tablet
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
|
Placebo Comparator: Phase2 Empagliflozin 10mg daily or placebo |
Drug: Empagliflozin Oral Tablet [Jardiance]
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
Drug: Placebo Oral Tablet
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
|
Outcome Measures
Primary Outcome Measures
- Reduction in cardiac sympathetic nerve activity [18 weeks]
Cardiac sympathetic nerve activity assessed by cardiac noradrenaline spillover
- Reduction in renal sympathetic nerve activity [18 weeks]
Renal sympathetic nerve activity assessed by renal noradrenaline spillover
- Reduction in muscle sympathetic nerve activity [18 weeks]
Muscle sympathetic nerve activity assessed by microneurography
Secondary Outcome Measures
- Reduction in ambulatory BP (blood pressure) [18 weeks]
Blood Pressure assessed by ambulatory blood pressure monitoring
- Reduction in central Blood Pressure [18 weeks]
central Blood Pressure assessed by Sphygmocor XCEL
- Change in urinary sodium excretion [18 weeks]
Urinary sodium excretion assessed in a 24 hour urine sample
- Change in glycemic control [18 weeks]
Glycemic control as assessed by an oral glucose tolerance test
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age: 25 -65 years
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(Body Mass Index) BMI≥30kg/m2
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Currently weight stable (+/- 3% in previous 6-12 months and not on any specific exercise or dietary program)
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Metabolic syndrome (defined as having: obesity (BMI ≥30kg/m2 ) plus any two of the following four factors: Elevated triglycerides (Triglyceride≥ 1.7mmol/L), Reduced HDL (High - density lipoprotein) cholesterol (<1.0mmol/L in males, <1.3mmol/L in females), Elevated clinic systolic (Blood Pressure) BP ≥130 or diastolic BP ≥85mmHg, Fasting glucose ≥5.6mmol/L or type 2 diabetes.
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office BP for screening purposes ≤160/90mmHg
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drug naïve for at least 6 weeks prior to baseline assessment
Exclusion Criteria:
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Grade 2-3 hypertension (systolic office BP >160, diastolic office BP >100 mmHg)
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Secondary causes of hypertension
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CKD (Chronic kidney disease) stage 4-5 {(estimated glomerular filtration) eGFR<30ml/min}
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Heart failure NYHA (New York Heart Association) class II-IV
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Recent CV (cardiovascular) event (acute myocardial infarction, acute coronary syndrome, stroke or transient ischaemic attack within the previous six months)
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unstable psychiatric condition
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medication such as corticosteroids, several antidepressants and antipsychotics
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Female participants of childbearing potential must have a negative pregnancy test prior to treatment
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Royal Perth Hospital | Perth | Western Australia | Australia | 6000 |
Sponsors and Collaborators
- Royal Perth Hospital
Investigators
- Principal Investigator: Markus Schlaich, MD,FAHA,FESC, Royal Perth Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
- 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. Epub 2006 Sep 25. Review.
- 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. Review.
- Mahfoud F, Schlaich M, Kindermann I, Ukena C, Cremers B, Brandt MC, Hoppe UC, Vonend O, Rump LC, Sobotka PA, Krum H, Esler M, Böhm 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.
- 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. Epub 2003 Jul 7.
- 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.
- 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.
- Sverrisdóttir YB, Jansson LM, Hägg 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.
- Ziegler D, Weise F, Langen KJ, Piolot R, Boy C, Hübinger A, Müller-Gärtner 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.
- 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.
- REG 16-157