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

Primary Purpose

Metabolic Syndrome, Type 2 Diabetes Mellitus, Obesity

Status

Recruiting

Phase

Phase 4

Locations

Australia

Study Type

Interventional

Intervention

Empagliflozin Oral Tablet [Jardiance]

Placebo Oral Tablet

About this trial

This is an interventional other trial for Metabolic Syndrome focused on measuring Metabolic Syndrome, Central sympathetic nervous system, Sodium-glucose co-transporter-2 (SGLT2), Blood Pressure

Eligibility Criteria

25 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Sites / Locations

Royal Perth HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Phase 1

Phase2

Arm Description

Empagliflozin 10mg daily or placebo

Outcomes

Primary Outcome Measures

Reduction in cardiac sympathetic nerve activity

Cardiac sympathetic nerve activity assessed by cardiac noradrenaline spillover

Reduction in renal sympathetic nerve activity

Renal sympathetic nerve activity assessed by renal noradrenaline spillover

Reduction in muscle sympathetic nerve activity

Muscle sympathetic nerve activity assessed by microneurography

Secondary Outcome Measures

Reduction in ambulatory BP (blood pressure)

Blood Pressure assessed by ambulatory blood pressure monitoring

Reduction in central Blood Pressure

central Blood Pressure assessed by Sphygmocor XCEL

Change in urinary sodium excretion

Urinary sodium excretion assessed in a 24 hour urine sample

Change in glycemic control

Glycemic control as assessed by an oral glucose tolerance test

Full Information

NCT ID

NCT03912909

First Posted

October 23, 2018

Last Updated

September 28, 2022

Sponsor

Royal Perth Hospital

1. Study Identification

Unique Protocol Identification Number

NCT03912909

Brief Title

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

Acronym

EMPA-SNS

Official Title

Effects of SGLT-2 Inhibition on Sympathetic Nervous System Activity in Humans

Study Type

Interventional

2. Study Status

Record Verification Date

September 2022

Overall Recruitment Status

Recruiting

Study Start Date

August 1, 2018 (Actual)

Primary Completion Date

March 31, 2024 (Anticipated)

Study Completion Date

December 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Royal Perth Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metabolic Syndrome, Type 2 Diabetes Mellitus, Obesity

Keywords

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

7. Study Design

Primary Purpose

Other

Study Phase

Phase 4

Interventional Study Model

Crossover Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Phase 1

Arm Type

Active Comparator

Arm Description

Empagliflozin 10mg daily or placebo

Arm Title

Phase2

Arm Type

Placebo Comparator

Arm Description

Empagliflozin 10mg daily or placebo

Intervention Type

Drug

Intervention Name(s)

Empagliflozin Oral Tablet [Jardiance]

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo Oral Tablet

Intervention Description

Primary Outcome Measure Information:

Title

Reduction in cardiac sympathetic nerve activity

Description

Cardiac sympathetic nerve activity assessed by cardiac noradrenaline spillover

Time Frame

18 weeks

Title

Reduction in renal sympathetic nerve activity

Description

Renal sympathetic nerve activity assessed by renal noradrenaline spillover

Time Frame

18 weeks

Title

Reduction in muscle sympathetic nerve activity

Description

Muscle sympathetic nerve activity assessed by microneurography

Time Frame

18 weeks

Secondary Outcome Measure Information:

Title

Reduction in ambulatory BP (blood pressure)

Description

Blood Pressure assessed by ambulatory blood pressure monitoring

Time Frame

18 weeks

Title

Reduction in central Blood Pressure

Description

central Blood Pressure assessed by Sphygmocor XCEL

Time Frame

18 weeks

Title

Change in urinary sodium excretion

Description

Urinary sodium excretion assessed in a 24 hour urine sample

Time Frame

18 weeks

Title

Change in glycemic control

Description

Glycemic control as assessed by an oral glucose tolerance test

Time Frame

18 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

25 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Anu Joyson, MSN

Phone

+61 8 92240390

anu.joyson@uwa.edu.au

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Markus Schlaich, MD,FAHA,FESC

Organizational Affiliation

Royal Perth Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Royal Perth Hospital

City

Perth

State/Province

Western Australia

ZIP/Postal Code

6000

Country

Australia

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Anu Joyson, MSC RN

Phone

=08 922

Ext

40390

anu.joyson@uwa.edu.au

First Name & Middle Initial & Last Name & Degree

Markus Schlaich, Prof

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

Individual Participant Data will not be shared to maintain anonymity and confidentiality of the participants

Citations:

PubMed Identifier

26378978

Citation

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 Reference

background

PubMed Identifier

12948431

Citation

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.

Results Reference

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PubMed Identifier

17000932

Citation

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.

Results Reference

background

PubMed Identifier

23271752

Citation

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.

Results Reference

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PubMed Identifier

23997009

Citation

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.

Results Reference

background

PubMed Identifier

12847071

Citation

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.

Results Reference

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PubMed Identifier

9562349

Citation

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.

Results Reference

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PubMed Identifier

20174639

Citation

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.

Results Reference

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PubMed Identifier

21518978

Citation

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.

Results Reference

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

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