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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03912909




Registration number
NCT03912909
Ethics application status
Date submitted
23/10/2018
Date registered
11/04/2019
Date last updated
15/04/2019

Titles & IDs
Public title
Effects of Sodium-glucose Co-transporter-2( SGLT-2 ) Inhibition on Sympathetic Nervous System Activity in Humans
Scientific title
Effects of SGLT-2 Inhibition on Sympathetic Nervous System Activity in Humans
Secondary ID [1] 0 0
REG 16-157
Universal Trial Number (UTN)
Trial acronym
EMPA-SNS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metabolic Syndrome 0 0
Type 2 Diabetes Mellitus 0 0
Obesity 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes
Metabolic and Endocrine 0 0 0 0
Metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Empagliflozin Oral Tablet [Jardiance]
Treatment: Drugs - Placebo Oral Tablet

Active Comparator: Phase 1 - Empagliflozin 10mg daily or placebo

Placebo Comparator: Phase2 - Empagliflozin 10mg daily or placebo


Treatment: Drugs: 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

Treatment: Drugs: 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

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Reduction in cardiac sympathetic nerve activity - Cardiac sympathetic nerve activity assessed by cardiac noradrenaline spillover
Timepoint [1] 0 0
18 weeks
Primary outcome [2] 0 0
Reduction in renal sympathetic nerve activity - Renal sympathetic nerve activity assessed by renal noradrenaline spillover
Timepoint [2] 0 0
18 weeks
Primary outcome [3] 0 0
Reduction in muscle sympathetic nerve activity - Muscle sympathetic nerve activity assessed by microneurography
Timepoint [3] 0 0
18 weeks
Secondary outcome [1] 0 0
Reduction in ambulatory BP (blood pressure) - Blood Pressure assessed by ambulatory blood pressure monitoring
Timepoint [1] 0 0
18 weeks
Secondary outcome [2] 0 0
Reduction in central Blood Pressure - central Blood Pressure assessed by Sphygmocor XCEL
Timepoint [2] 0 0
18 weeks
Secondary outcome [3] 0 0
Change in urinary sodium excretion - Urinary sodium excretion assessed in a 24 hour urine sample
Timepoint [3] 0 0
18 weeks
Secondary outcome [4] 0 0
Change in glycemic control - Glycemic control as assessed by an oral glucose tolerance test
Timepoint [4] 0 0
18 weeks

Eligibility
Key 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
Minimum age
25 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Other
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 4
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
6000 - Perth

Funding & Sponsors
Primary sponsor type
Other
Name
Royal Perth Hospital
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03912909
Trial related presentations / publications
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.
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.
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.
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.
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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Markus Schlaich, MD,FAHA,FESC
Address 0 0
Royal Perth Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Anu Joyson, MSN
Address 0 0
Country 0 0
Phone 0 0
+61 8 92240390
Fax 0 0
Email 0 0
anu.joyson@uwa.edu.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03912909