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

Sponsor
Royal Perth Hospital (Other)
Overall Status
Recruiting
CT.gov ID
NCT03912909
Collaborator
(none)
30
1
2
53
0.6

Study Details

Study Description

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
  • 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.

Study Design

Study Type:
Interventional
Anticipated 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 :
Aug 1, 2018
Anticipated Primary Completion Date :
Mar 31, 2022
Anticipated Study Completion Date :
Dec 30, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

  1. Reduction in cardiac sympathetic nerve activity [18 weeks]

    Cardiac sympathetic nerve activity assessed by cardiac noradrenaline spillover

  2. Reduction in renal sympathetic nerve activity [18 weeks]

    Renal sympathetic nerve activity assessed by renal noradrenaline spillover

  3. Reduction in muscle sympathetic nerve activity [18 weeks]

    Muscle sympathetic nerve activity assessed by microneurography

Secondary Outcome Measures

  1. Reduction in ambulatory BP (blood pressure) [18 weeks]

    Blood Pressure assessed by ambulatory blood pressure monitoring

  2. Reduction in central Blood Pressure [18 weeks]

    central Blood Pressure assessed by Sphygmocor XCEL

  3. Change in urinary sodium excretion [18 weeks]

    Urinary sodium excretion assessed in a 24 hour urine sample

  4. Change in glycemic control [18 weeks]

    Glycemic control as assessed by an oral glucose tolerance test

Eligibility Criteria

Criteria

Ages Eligible for Study:
25 Years to 65 Years
Sexes Eligible for Study:
All
Accepts 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Royal Perth Hospital Perth Western Australia Australia 6000

Sponsors and Collaborators

  • Royal Perth Hospital

Investigators

  • Principal Investigator: Markus Schlaich, MD,FAHA,FESC, Royal Perth Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Dr Markus Schlaich, Principal Investigator, Royal Perth Hospital
ClinicalTrials.gov Identifier:
NCT03912909
Other Study ID Numbers:
  • REG 16-157
First Posted:
Apr 11, 2019
Last Update Posted:
Sep 27, 2021
Last Verified:
Sep 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Dr Markus Schlaich, Principal Investigator, Royal Perth Hospital
Additional relevant MeSH terms:

Study Results

No Results Posted as of Sep 27, 2021