Metabolic Syndrome, Obesity, Type 2 Diabetes Mellitus
Conditions
Keywords
Metabolic Syndrome, Central sympathetic nervous system, Sodium-glucose co-transporter-2 (SGLT2), Blood Pressure
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.
Interventions
DRUGEmpagliflozin 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
DRUGPlacebo 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
Sponsors
Royal Perth Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
25 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reduction in cardiac sympathetic nerve activity | 18 weeks | Cardiac sympathetic nerve activity assessed by cardiac noradrenaline spillover |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Reduction in ambulatory BP (blood pressure) | 18 weeks | Blood Pressure assessed by ambulatory blood pressure monitoring |
| Change in glycemic control | 18 weeks | Glycemic control as assessed by an oral glucose tolerance test |
| Reduction in central Blood Pressure | 18 weeks | central Blood Pressure assessed by Sphygmocor XCEL |
| Change in urinary sodium excretion | 18 weeks | Urinary sodium excretion assessed in a 24 hour urine sample |
Countries
Australia
Contacts
Primary ContactAnu Joyson, MSN
Outcome results
None listed