Effects of Sodium-glucose Co-transporter-2( SGLT-2 ) Inhibition on Sympathetic Nervous System Activity in Humans
- Conditions
- Metabolic SyndromeType 2 Diabetes MellitusObesity
- Interventions
- Drug: Placebo Oral Tablet
- Registration Number
- NCT03912909
- Lead Sponsor
- 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.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 30
- 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
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Phase 1 Placebo Oral Tablet Empagliflozin 10mg daily or placebo Phase2 Placebo Oral Tablet Empagliflozin 10mg daily or placebo Phase 1 Empagliflozin Oral Tablet [Jardiance] Empagliflozin 10mg daily or placebo Phase2 Empagliflozin Oral Tablet [Jardiance] Empagliflozin 10mg daily or placebo
- Primary Outcome Measures
Name Time Method Reduction in renal sympathetic nerve activity 18 weeks Renal sympathetic nerve activity assessed by renal noradrenaline spillover
Reduction in muscle sympathetic nerve activity 18 weeks Muscle sympathetic nerve activity assessed by microneurography
Reduction in cardiac sympathetic nerve activity 18 weeks Cardiac sympathetic nerve activity assessed by cardiac noradrenaline spillover
- Secondary Outcome Measures
Name Time Method Reduction in ambulatory BP (blood pressure) 18 weeks Blood Pressure assessed by ambulatory blood pressure monitoring
Change in urinary sodium excretion 18 weeks Urinary sodium excretion assessed in a 24 hour urine sample
Reduction in central Blood Pressure 18 weeks central Blood Pressure assessed by Sphygmocor XCEL
Change in glycemic control 18 weeks Glycemic control as assessed by an oral glucose tolerance test
Trial Locations
- Locations (1)
Royal Perth Hospital
🇦🇺Perth, Western Australia, Australia