Effects of SGLT2 Inhibitor on Hemodynamic Parameters in Resistant Hypertensive Subjects

Phase 4

Completed

• Conditions: Diabetes Mellitus, Type 2; Hypertension; Blood Pressure; Microalbuminuria; Obesity; Cardiac Hypertrophy; Vascular Stiffness
• Interventions: Drug: Dapagliflozin 10mg; Drug: Glibenclamide 5Mg Tablet

• Registration Number: NCT03089333
• Lead Sponsor: University of Campinas, Brazil

Brief Summary

New strategies trying to achieve blood pressure control and consequently reduce cardiovascular risk in resistant hypertensive subjects are promising. In this context, the SGLT2 inhibitor dapagliflozin, not yet investigated in resistant hypertension, arises as a potential drug in order to impact on blood pressure levels, as well as target organ damage and adiposity in this high-risk population.

Detailed Description

Objective: The investigators aim to assess whether the intervention with the SGLT2 inhibitor -dapaglifozin - reduces PA levels, target organ damage, fat profile and change the adipokines levels in patients with resistant hypertension with DM2. Methods and design: This crossover randomized, double-blind, interventional study controlled by standard therapy will include 20 patients with resistant hypertension and type 2 diabetes, followed in Outpatient Clinic specialized in Resistant Hypertension at clinical Hospital-UNICAMP. They will be randomly assigned into two groups (1) initially treated with dapagliflozin in combination with their usual antihypertensive therapy and metformin, at 12 weeks (n = 10) or group (2) Control initially treated with glibenclamide at a dose of 5mg daily in combination with antihypertensive therapy usual and metformin, at 12 weeks (n = 10). Office ambulatory and home BP measurements; anthropometric measurements, determination of vascular stiffness by pulse wave velocity, echocardiogram, body bioimpedance, enzyme immunoassays for the determination of adipokines, and lab tests to evaluate biochemical parameters will be performed pre- and after the use of both treatments. Glycemic parameters, and weight will be assessed every 4 weeks. Results and conclusion: The use of SGLT2 inhibitor in these patients may provide new strategies for treatment of patients with resistant hypertension.

Study Timeline

• Study Start: 2016-07
• Study First Submitted: 2017-03-20
• Study First Submitted QC: 2017-03-20
• Study First Posted: 2017-03-24
• Primary Completion: 2017-10
• Study Completion: 2017-12
• Status Verified: 2018-05
• Last Update Submitted: 2018-05-02
• Last Update Posted: 2018-05-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

• Resistant hypertension and type 2 diabetes diagnoses after a 6-month follow-up
• Use of metformin therapy
• Therapy adherence
• Agree to participate in the research protocol and sign the informed consent form

Exclusion Criteria

• secondary Hypertension
• pseudoresistance hypertension (poor medication adherence and white coat hypertension)
• patients with symptomatic ischemic heart disease, impaired renal function, liver disease and history of stroke, myocardial infarction and peripheral vascular diseases
• pregnancy
• smoking
• autoimmune diseases

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Glibenclamide	Glibenclamide 5Mg Tablet	Glibenclamide 5mg daily for 12 weeks.
Dapagliflozin	Dapagliflozin 10mg	Dapagliflozin 10mg daily for 12 weeks.
Dapagliflozin	Glibenclamide 5Mg Tablet	Dapagliflozin 10mg daily for 12 weeks.
Glibenclamide	Dapagliflozin 10mg	Glibenclamide 5mg daily for 12 weeks.

Primary Outcome Measures

Name	Time	Method
Change in Systolic Blood Pressure	Baseline and 12 weeks	Change in Office Systolic Blood Pressure after 12 weeks of treatment

Secondary Outcome Measures

Name	Time	Method
Change in arterial stiffness	Baseline and 12 weeks	Change in arterial stiffness measured by Sphygmocor device
Change in left ventricular hypertrophy	Baseline and 12 weeks	Change in left ventricular hypertrophy measured by Echocardiogram
Change in Ambulatory Systolic Blood Pressure	Baseline and 12 weeks	Change in Ambulatory Systolic Blood Pressure after 12 weeks of treatment
Change in weight	Baseline and 12 weeks	Change in body weight
Change in microalbuminuria	Baseline and 12 weeks	Change in microalbuminuria measured by Urine Albumin/Creatinine Ratio

Trial Locations

Locations (1)

University of Campinas (UNICAMP); 🇧🇷 Campinas, São Paulo, Brazil