Dapagliflozin on Blood Pressure Variability and Ambulatory Arterial Stiffness Index in Hypertension

Effect of Dapagliflozin on the Blood Pressure Variability and the Ambulatory Arterial Stiffness Index in Individuals With Stage I Hypertension Without Diabetes Mellitus

The prevalence of arterial hypertension has remained the same in the last 5 years, however, almost 50% of the population continues without an adequate adjustment according to the National Health Survey of the Midway 2016.

It has been shown that the variability of blood pressure (VBP) during 24 h and visit-visit is associated with cardiovascular diseases (CVD) over the effect of blood pressure (BP) itself. On the other hand, arterial stiffness is well known as an independent factor of CVD risk and for its evaluation the ambulatory arterial stiffness index (AASI) has been proposed. AASI and the VPA obtained through an evaluation by ambulatory BP monitoring (ABPM) individual of 24 h.

Dapagliflozin is an inhibitor of the sodium-glucose cotransporter type 2 (iSGLT2) for the treatment of diabetes mellitus type 2 (DM2) that promotes natriuresis and osmotic diuresis, which produces a decrease in plasma volume and a decrease in BP.

The aim of ths study is to evaluate the effect of dapagliflozin on VBP and AASI in individuals with stage I hypertension whitout DM2.

The investigators hypothesis is that the administration of dapagliflozin decreases the VBP and AASI in individuals with stage I hypertension whitout DM2.

Study Overview

• Status: Unknown
• Conditions: Hypertension
• Intervention / Treatment: Drug: Dapagliflozin; Drug: Placebo - Cap

Detailed Description

A randomized, double-blind, placebo-controlled clinical trial in 20 patients with a diagnosis of stage I hypertension without DM2.

They will be assigned randomly two groups of 10 patients each to receive 10 mg of Dapagliflozin (Forxiga, Astra Zeneca) or placebo, one per day before breakfast during 12 weeks.

There will be calculated indices of VBP: 24 h, daytime and night-time standard deviation (SD), coefficient of variation (CV), 24 h weighted SD, Day-to-nigth BP changes and average real variability (AVR). On the other hand, AASI will be calculated with a linear regression.

This protocol it's already approved by the local ethics committee and written informed consent it's going to be obtained from all volunteers.

Statistical analysis will be presented through measures of central tendency and dispersion, average and deviation standard for quantitative variables; frequencies and percentages for variable qualitative. Qualitative variables will be analyzed by X2 o exact fisher test, will be used for differences inter-group. Mann-Whitney U Test and Wilcoxon Test for the within-groups differences. It will be considered statistical significance p ≤0.05.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Manuel Gonzalez, PhD; Phone Number: 34212 +52-10-58-52-00; Email: uiec@prodigy.net.mx
• Study Contact Backup: Name: LIZET YADIRA ROSALES, PhD; Phone Number: 34212 +52-10-58-52-00; Email: lizet.rosales@gmail.com

Study Locations

• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44340
      • Recruiting
      • Instituto de Terapeútica Experimental y Clínica. Centro Universitario de Ciencias de la Salud. Universidad de Guadalajara
      • Contact: Manuel Gonzalez, PhD; Phone Number: 34212 +52-10-58-52-00; Email: uiec@prodigy.net.mx

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 28 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Informed consent signed
• Patients both sexes, age between 30 and 60 years
• Diagnosis of stage I hypertension according ACC/AHA (American college of cardiology/American heart association) blood pressure between 130-139/ 80-89 mmHg.
• Fasting plasma glucose < 100 mg/dl
• BMI >35 kg/m2
• Glomerular filtration rate > 60ml/min/1.73m2

Exclusion Criteria:

• Women with confirmed or suspected pregnancy
• Women under lactation and/or puerperium
• Hypersensibility to ingredients of intervention
• Physical impossibility for taking pills
• Known uncontrolled renal, hepatic, heart, thyroid or cardiovascular diseased
• Previous treatment for hypertension or depression
• Triglycerides ≥ 400 mg/dl
• Total cholesterol ≥ 240 mg/dl
• Worker per shift night
• Arrhythmia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dapagliflozin; Dapagliflozin capsules, 10 mg, one per day before breakfast during 12 weeks.	Drug: Dapagliflozin; 10 mg, one per day before breakfast during 12 weeks.; Other Names: Forxiga
Placebo Comparator: Placebo; Placebo capsules, one per day before breakfast during 12 weeks.	Drug: Placebo - Cap; One per day before breakfast during 12 weeks.; Other Names: Calcined magnesium

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Indices of blood pressure: 24 h, daytime and night-time SD and CV, 24 h weighted SD, day-to-nigth BP changes and ARV	Blood pressure variability will be evaluated with ambulatory blood pressure monitoring	Baseline to Week 12
Ambulatory arterial stiffness index	Arterial stiffness will be evaluated with ambulatory blood pressure monitoring	Baseline to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulse Pressure of 24 h	Will be evaluated with ambulatory blood pressure monitoring, systolic BP minus diastolic BP.	Baseline to Week 12
Mean arterial pressure of 24 h, daytime and nigth-time	Will be evaluated with ambulatory blood pressure monitoring, systolic BP minus diastolic BP/3, plus diastolic BP.	Baseline to Week 12
Heart rate of 24 h, daytime and nigth-time	Will be evaluated with ambulatory blood pressure monitoring.	Baseline to Week 12
Hypertensive load daytime and nigth-time	Will be evaluated with ambulatory blood pressure monitoring.	Baseline to Week 12
White coat hypertension	will be evaluated with ambulatory blood pressure monitoring	Baseline to Week 12
Fasting glucose levels	The fasting glucose levels will be evaluated at baseline and week 12 with enzymatic/colorimetric techniques and the entered values reflect the fasting glucose level at week 12.	Baseline to Week 12
Total cholesterol	Total cholesterol levels will be evaluated at baseline and week 12 by enzymatic/colorimetric techniques and the entered values reflect the total cholesterol level at week 12	Baseline to Week 12
Triglycerides levels	Triglycerides levels will be evaluated at baseline and week 12 with enzymatic/colorimetric techniques and the entered values reflect the triglycerides level at week 12	Baseline to Week 12
High density lipoprotein (c-HDL) levels	c-HDL levels will be evaluated at baseline and week 12 with enzymatic/colorimetric techniques and the entered values reflect the c-HDL level at week 12	Baseline to Week 12
Creatinine levels	Creatinine levels will be evaluated at baseline and week 12 with enzymatic/colorimetric techniques	Baseline to Week 12
Uric acid levels	Uric acid levels will be evaluated at baseline and week 12 with enzymatic/colorimetric techniques	Baseline to Week 12
Body Weight	The body weight will be measured at baseline, week 4, week 8 and week 12 with a bioimpedance balance and the entered values reflect the body weight at week 12	Baseline, week 4, week 8 and week 12
Body Mass Index	Body Mas Index will be calculated at baseline, week 4, week 8 and week 12 with the Quetelet index formula and the entered values reflect the body mass index at week 12	Baseline, week 4, week 8 and week 12
Waist circumference	Waist circumference will be evaluated with the method proposed by ISAK.	Baseline, week 4, week 8 and week 12
Glomerular filtration rate	Glomerular filtration rate will be calculated at baseline and week 12 with the Cockcroft-Gault formula and the entered values reflect the Glomerular filtration rate at week 12	Baseline to Week 12

Collaborators and Investigators

• Sponsor: University of Guadalajara
• Investigators: Principal Investigator: MANUEL GONZALEZ, PhD, University of Guadalajara

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2019
• Primary Completion (Anticipated): April 1, 2021
• Study Completion (Anticipated): July 1, 2021

Study Registration Dates

• First Submitted: July 9, 2018
• First Submitted That Met QC Criteria: July 9, 2018
• First Posted (Actual): July 19, 2018

Study Record Updates

• Last Update Posted (Actual): December 28, 2020
• Last Update Submitted That Met QC Criteria: December 23, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Variability of blood pressure; ABPM; Dapagliflozin; Stage I Hypertension; Without type 2 diabetes mellitus; Ambulatory arterial stiffness index
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin
• Other Study ID Numbers: DAPA on VBP-AASI Hypertension

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No