Clinical trial NCT03592667: Dapagliflozin on Blood Pressure Variability and Ambulatory Arterial Stiffness Index in Hypertension
Official title: Effect of Dapagliflozin on the Blood Pressure Variability and the Ambulatory Arterial Stiffness Index in Individuals With Stage I Hypertension Without Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Hypertension
Keywords: Stage I Hypertension
Without type 2 diabetes mellitus
Variability of blood pressure
Ambulatory arterial stiffness index
Dapagliflozin
ABPM
Lead sponsor: University of Guadalajara
Sponsor class: OTHER
First posted: 2018-07-19
Enrollment: 20
Sex: ALL
Minimum age (years): 30
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Indices of blood pressure: 24 h, daytime and night-time SD and CV, 24 h weighted SD, day-to-nigth BP changes and ARV
timeFrame: Baseline to Week 12
measure: Ambulatory arterial stiffness index
timeFrame: Baseline to Week 12
Secondary outcomes:
measure: Pulse Pressure of 24 h
timeFrame: Baseline to Week 12
measure: Mean arterial pressure of 24 h, daytime and nigth-time
timeFrame: Baseline to Week 12
measure: Heart rate of 24 h, daytime and nigth-time
timeFrame: Baseline to Week 12
measure: Hypertensive load daytime and nigth-time
timeFrame: Baseline to Week 12
measure: White coat hypertension
timeFrame: Baseline to Week 12
measure: Fasting glucose levels
timeFrame: Baseline to Week 12
measure: Total cholesterol
timeFrame: Baseline to Week 12
measure: Triglycerides levels
timeFrame: Baseline to Week 12
measure: High density lipoprotein (c-HDL) levels
timeFrame: Baseline to Week 12
measure: Creatinine levels
timeFrame: Baseline to Week 12
measure: Uric acid levels
timeFrame: Baseline to Week 12
measure: Body Weight
timeFrame: Baseline, week 4, week 8 and week 12
measure: Body Mass Index
timeFrame: Baseline, week 4, week 8 and week 12
measure: Waist circumference
timeFrame: Baseline, week 4, week 8 and week 12
measure: Glomerular filtration rate
timeFrame: Baseline to Week 12
Other outcomes:
Locations:
city: Guadalajara
country: Mexico
facility: Instituto de Terapeútica Experimental y Clínica. Centro Universitario de Ciencias de la Salud. Universidad de Guadalajara
state: Jalisco
Study officials:
affiliation: University of Guadalajara
name: MANUEL GONZALEZ, PhD
role: PRINCIPAL_INVESTIGATOR
References: