Effects of Sodium-glucose Co-transporter-2( SGLT-2 ) Inhibition on Sympathetic Nervous System Activity in Humans

NCT03912909 | Unknown Phase 4

• 1 other identifier: REG 16-157
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Metabolic Syndrome; Type 2 Diabetes Mellitus; Obesity

Keywords

Metabolic Syndrome; Central sympathetic nervous system; Sodium-glucose co-transporter-2 (SGLT2); Blood Pressure

Outcome Measures

Primary Outcomes (3)

• 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

Secondary Outcomes (4)

• Reduction in ambulatory BP (blood pressure)

  18 weeks

• Reduction in central Blood Pressure

  18 weeks

• Change in urinary sodium excretion

  18 weeks

• Change in glycemic control

  18 weeks

Study Arms (2)

Phase 1

ACTIVE COMPARATOR

Empagliflozin 10mg daily or placebo

Drug: Empagliflozin Oral Tablet [Jardiance]; Drug: Placebo Oral Tablet

Phase2

PLACEBO COMPARATOR

Empagliflozin 10mg daily or placebo

Drug: Empagliflozin Oral Tablet [Jardiance]; Drug: Placebo Oral Tablet

Interventions

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

Phase 1; Phase2

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

Phase 1; Phase2

Eligibility Criteria

• Age: 25 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 25 -65 years
• (Body Mass Index) BMI≥30kg/m2
• Currently weight stable (+/- 3% in previous 6-12 months and not on any specific exercise or dietary program)
• 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.
• office BP for screening purposes ≤160/90mmHg
• drug naïve for at least 6 weeks prior to baseline assessment

You may not qualify if:

• Grade 2-3 hypertension (systolic office BP \>160, diastolic office BP \>100 mmHg)
• Secondary causes of hypertension
• CKD (Chronic kidney disease) stage 4-5 {(estimated glomerular filtration) eGFR\<30ml/min}
• Heart failure NYHA (New York Heart Association) class II-IV
• Recent CV (cardiovascular) event (acute myocardial infarction, acute coronary syndrome, stroke or transient ischaemic attack within the previous six months)
• unstable psychiatric condition
• medication such as corticosteroids, several antidepressants and antipsychotics
• Female participants of childbearing potential must have a negative pregnancy test prior to treatment

Sponsors & Collaborators

• Royal Perth Hospital: lead

Study Sites (1)

Royal Perth Hospital

Perth, Western Australia, 6000, Australia

RECRUITING

Related Publications (9)

• 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.

  PMID: 26378978 BACKGROUND

• 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.

  PMID: 12948431 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.

  PMID: 17000932 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.

  PMID: 23271752 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.

  PMID: 23997009 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.

  PMID: 12847071 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.

  PMID: 9562349 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.

  PMID: 20174639 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.

  PMID: 21518978 BACKGROUND

MeSH Terms

Conditions

Metabolic Syndrome; Diabetes Mellitus, Type 2; Obesity

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Diabetes Mellitus; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Markus Schlaich, MD,FAHA,FESC

  Royal Perth Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anu Joyson, MSN

CONTACT

+61 8 92240390; anu.joyson@uwa.edu.au

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 23, 2018
• First Posted: April 11, 2019
• Study Start: August 1, 2018
• Primary Completion: March 31, 2024
• Study Completion: December 30, 2024
• Last Updated: September 29, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)