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Metabolic SyndromePhase 4EMPA-SNSNCT03912909

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

A Phase 4 study testing Empagliflozin Oral Tablet [Jardiance] in people with Metabolic Syndrome and Type 2 Diabetes Mellitus, run by Royal Perth Hospital at 1 site in Australia.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 25 to 65 years
What is being tested?
Empagliflozin Oral Tablet [Jardiance]
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
30 participants
Where
1 siteAustralia
Study dates
1 Aug 2018to 30 Dec 2024
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 25 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

Australia1 site, 1 recruiting
  • Royal Perth Hospital

    Perth, Western Australia, 6000

    Anu Joyson, MSC RN, =08 922 ext. 40390, anu.joyson@uwa.edu.au

    Markus Schlaich, Prof

    Recruiting

Other trials in Australia

About this study

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

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.

Read the 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.

Being tested
Empagliflozin Oral Tablet [Jardiance], Placebo Oral Tablet
Keywords
Metabolic Syndrome, Central sympathetic nervous system, Sodium-glucose co-transporter-2 (SGLT2), Blood Pressure
Medical subject headings
Metabolic Syndrome, Diabetes Mellitus, Type 2, Obesity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 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

  • Placebo Oral TabletDrug

    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

Study groups in NCT03912909
Study groupRoleWhat they receive
Phase 1Active comparatorEmpagliflozin 10mg daily or placebo
Receives: Drug: Empagliflozin Oral Tablet [Jardiance]; Drug: Placebo Oral Tablet
Phase2Placebo comparatorEmpagliflozin 10mg daily or placebo
Receives: Drug: Empagliflozin Oral Tablet [Jardiance]; Drug: Placebo Oral Tablet

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Reduction in cardiac sympathetic nerve activity

    Cardiac sympathetic nerve activity assessed by cardiac noradrenaline spillover

    Measured: 18 weeks

  2. Reduction in renal sympathetic nerve activity

    Renal sympathetic nerve activity assessed by renal noradrenaline spillover

    Measured: 18 weeks

  3. Reduction in muscle sympathetic nerve activity

    Muscle sympathetic nerve activity assessed by microneurography

    Measured: 18 weeks

Secondary outcomes (4)
  1. Reduction in ambulatory BP (blood pressure)

    Blood Pressure assessed by ambulatory blood pressure monitoring

    Measured: 18 weeks

  2. Reduction in central Blood Pressure

    central Blood Pressure assessed by Sphygmocor XCEL

    Measured: 18 weeks

  3. Change in urinary sodium excretion

    Urinary sodium excretion assessed in a 24 hour urine sample

    Measured: 18 weeks

  4. Change in glycemic control

    Glycemic control as assessed by an oral glucose tolerance test

    Measured: 18 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Apr 2019
  2. Study start1 Aug 2018
  3. Primary completion31 Mar 2024 (estimated)
  4. Study completion30 Dec 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Other
Allocation
Randomised
Intervention model
Crossover
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03912909
Sponsor's protocol ID
REG 16-157
Acronym
EMPA-SNS
Status last verified
Sep 2022
First submitted
23 Oct 2018
Last updated
29 Sep 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Individual Participant Data will not be shared to maintain anonymity and confidentiality of the participants

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.

    PubMed 26378978
  • 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.

    PubMed 12948431
  • 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.

    PubMed 17000932
  • 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.

    PubMed 23271752
  • 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.

    PubMed 23997009
  • 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.

    PubMed 12847071
  • 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.

    PubMed 9562349
  • 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.

    PubMed 20174639
  • 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.

    PubMed 21518978

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Empagliflozin Oral Tablet [Jardiance] in people with Metabolic Syndrome and Type 2 Diabetes Mellitus, run by Royal Perth Hospital at 1 site in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 29 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Anu Joyson, MSN (+61 8 92240390, anu.joyson@uwa.edu.au), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Reduction in cardiac sympathetic nerve activity (time frame: 18 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03912909, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2022.

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