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

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ClinicalTrials.gov Identifier: NCT03912909
Recruitment Status : Recruiting
First Posted : April 11, 2019
Last Update Posted : April 15, 2019
Sponsor:
Information provided by (Responsible Party):
Professor Markus Schlaich, Royal Perth Hospital

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
Metabolic Syndrome Type 2 Diabetes Mellitus Obesity Drug: Empagliflozin Oral Tablet [Jardiance] Drug: Placebo Oral Tablet 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Other
Official Title: Effects of SGLT-2 Inhibition on Sympathetic Nervous System Activity in Humans
Actual Study Start Date : August 1, 2018
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : March 30, 2020

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Reduction in cardiac sympathetic nerve activity [ Time Frame: 18 weeks ]
    Cardiac sympathetic nerve activity assessed by cardiac noradrenaline spillover

  2. Reduction in renal sympathetic nerve activity [ Time Frame: 18 weeks ]
    Renal sympathetic nerve activity assessed by renal noradrenaline spillover

  3. Reduction in muscle sympathetic nerve activity [ Time Frame: 18 weeks ]
    Muscle sympathetic nerve activity assessed by microneurography


Secondary Outcome Measures :
  1. Reduction in ambulatory BP (blood pressure) [ Time Frame: 18 weeks ]
    Blood Pressure assessed by ambulatory blood pressure monitoring

  2. Reduction in central Blood Pressure [ Time Frame: 18 weeks ]
    central Blood Pressure assessed by Sphygmocor XCEL

  3. Change in urinary sodium excretion [ Time Frame: 18 weeks ]
    Urinary sodium excretion assessed in a 24 hour urine sample

  4. Change in glycemic control [ Time Frame: 18 weeks ]
    Glycemic control as assessed by an oral glucose tolerance test



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Ages Eligible for Study:   25 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03912909


Contacts
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Contact: Anu Joyson, MSN +61 8 92240390 anu.joyson@uwa.edu.au

Locations
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Australia, Western Australia
Royal Perth Hospital Recruiting
Perth, Western Australia, Australia, 6000
Contact: Anu Joyson, MSC RN    =08 922 ext 40390    anu.joyson@uwa.edu.au   
Principal Investigator: Markus Schlaich, Prof         
Sponsors and Collaborators
Royal Perth Hospital
Investigators
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Principal Investigator: Markus Schlaich, MD,FAHA,FESC Royal Perth Hospital

Publications:

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Responsible Party: Professor Markus Schlaich, Principal Investigator, Royal Perth Hospital
ClinicalTrials.gov Identifier: NCT03912909     History of Changes
Other Study ID Numbers: REG 16-157
First Posted: April 11, 2019    Key Record Dates
Last Update Posted: April 15, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Individual Participant Data will not be shared to maintain anonymity and confidentiality of the participants

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Professor Markus Schlaich, Royal Perth Hospital:
Metabolic Syndrome
Central sympathetic nervous system
Sodium-glucose co-transporter-2 (SGLT2)
Blood Pressure
Additional relevant MeSH terms:
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Metabolic Syndrome
Glucose Metabolism Disorders
Metabolic Diseases
Insulin Resistance
Hyperinsulinism
Empagliflozin
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents
Physiological Effects of Drugs