Effects of SGLT2 Inhibitor on Hemodynamic Parameters in Resistant Hypertensive Subjects

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effects of Dapagliflozin, an SGLT2 Inhibitor, on Hemodynamic Parameters, Target Organ Damage and Obesity Profile in Resistant Hypertensive Subjects

Conditions
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Hypertension, Diabetes Mellitus, Type 2, Blood Pressure, Obesity, Cardiac Hypertrophy, Microalbuminuria, Vascular Stiffness

Intervention / Treatment
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* Drug: Dapagliflozin 10mg
* Drug: Glibenclamide 5Mg Tablet


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Two-way crossover design
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dapagliflozin<br>Dapagliflozin 10mg daily for 12 weeks. | Drug: Dapagliflozin 10mg<br>* Dapagliflozin at a dose of 10mg daily in combination with metoformin and current antihypertensive therapy for 12 weeks<br>* Other names: FARXIGA®;Drug: Glibenclamide 5Mg Tablet<br>* Glibenclamide at a dose of 5mg daily in combination with metoformin and current antihypertensive therapy for 12 weeks<br>* Other names: Glibenclamide;|
| Active Comparator: Glibenclamide<br>Glibenclamide 5mg daily for 12 weeks. | Drug: Dapagliflozin 10mg<br>* Dapagliflozin at a dose of 10mg daily in combination with metoformin and current antihypertensive therapy for 12 weeks<br>* Other names: FARXIGA®;Drug: Glibenclamide 5Mg Tablet<br>* Glibenclamide at a dose of 5mg daily in combination with metoformin and current antihypertensive therapy for 12 weeks<br>* Other names: Glibenclamide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Systolic Blood Pressure | Change in Office Systolic Blood Pressure after 12 weeks of treatment | Baseline and 12 weeks | 

Secondary Outcome Measures

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