Effect of Dapagliflozin on Blood Pressure Variability in Prediabetes and Prehypertension

Effect of Dapagliflozin on Blood Pressure Variability in Patients With Prediabetes and Prehypertension Without Pharmacological Treatment

Prediabetes is defined as an intermediate metabolic state that leads to the development of type 2 diabetes mellitus (DM2) and the prehypertension is a category assigned to identify patients who are at risk of developing hypertension (AH), in both pathologies the abnormalities in the variation of blood pressure (BP) has been related to organ damage, its evaluation is performed by ambulatory blood pressure monitoring (ABPM).

Dapagliflozin is a selective and reversible inhibitor of the sodium-glucose co-transporter type 2 (SGLT-2), which reduces renal reabsorption of glucose and promotes the excretion of glucose through the urine, in the way that glucose blood. Another reported effects is the decrease on BP, so it would be interesting to evaluate this effects in patients with prediabetes and prehypertension, as a potential therapy to treat disorders and to prevent progression to DM2 and Hypertension, respectively.

The aim of this study is to evaluate the effect of Dapagliflozin on variability of blood pressure in patients with prediabetes and prehypertension without pharmacological treatment.

The investigators hypothesis is that the administration of dapagliflozin decreases variability of blood pressure in patients with prediabetes and prehypertension without pharmacological treatment.

Study Overview

• Status: Completed
• Conditions: PreDiabetes; Prehypertension
• Intervention / Treatment: Drug: Dapagliflozin; Drug: Placebo - Cap

Detailed Description

A randomized, double-blind, placebo-controlled clinical trial in 30 patients with a diagnosis of prediabetes and prehypertension without treatment.

They will be assigned randomly two groups of 15 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 body mass index (BMI) and blood pressure variability. 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/ exact fisher test, will be used for differences inter-group Mann-Whitney U Test and coefficient of variation, Wilcoxon Test and index of variability for the within-groups differences. It will be considered statistical significance p ≤0.05.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44340
      • Instituto de Terapeútica Experimental y Clínica. Centro Universitario de Ciencias de la Salud. Universidad de Guadalajara

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 60 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 prediabetes according American Diabetes Association criteria (fasting blood glucose levels between 100-126 mg/dl; postprandial blood glucose levels after an oral glucose tolerance test with 75 of oral glucose between 140-199 mg/dl; or glycosylated hemoglobin between 5.7-6.4%)
• Diagnosis of prehypertension according (JNC8) Eighth Joint National Committee blood pressure between 120-139/ 80-89 mmHg.

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 or thyroid diseased
• Diabetes diagnosis
• Previous treatment for glucose or blood pressure Triglycerides ≥400 mg/dL
• Total cholesterol ≥240 mg/dL
• History of cardiovascular disease
• Worker per shift / night

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
24-hours Systolic Blood Pressure at Week 12	Blood pressure variability was evaluated with ambulatory blood pressure monitoring (ABPM) for 24 hours by oscillometric method Microlife WatchBP O3	Week 12
24-hours Diastolic Blood Pressure at Week 12	Blood pressure variability was evaluated with ambulatory blood pressure monitoring (ABPM) for 24 hours by oscillometric method Microlife WatchBP O3	Week 12
Daytime Systolic Blood Pressure at Week 12	Blood pressure variability was evaluated with ambulatory blood pressure monitoring (ABPM) from 8 am. to 11 p.m. by oscillometric method Microlife WatchBP O3	Week 12
Daytime Diastolic Blood Pressure at Week 12	Blood pressure variability was evaluated with ambulatory blood pressure monitoring (ABPM) from 8 a.m. to p.m. by oscillometric method Microlife WatchBP O3	Week 12
Nighttime Systolic Blood Pressure at Week 12	Blood pressure variability was evaluated with ambulatory blood pressure monitoring (ABPM) from 11 p.m to 8 a.m. by oscillometric method Microlife WatchBP O3	Week 12
Nighttime Diastolic Blood Pressure at Week 12	Blood pressure variability was evaluated with ambulatory blood pressure monitoring (ABPM) from 11 p.m. to 8 a.m. by oscillometric method Microlife WatchBP O3	Week 12
Systolic Blood Pressure Weighted Standard Deviation at Week 12	Blood pressure variability will be evaluated with ambulatory blood pressure monitoring (ABPM) for 24 hours by oscillometric method Microlife WatchBP O3	Week 12
Diastolic Blood Pressure Weighted Standard Deviation at Week 12	Blood pressure variability was evaluated with ambulatory blood pressure monitoring (ABPM) for 24 hours by oscillometric method Microlife WatchBP O3	Week 12
Coefficient of Variation of 24-hours, Systolic Blood Pressure at Week 12	Blood pressure variability was evaluated with ambulatory blood pressure monitoring (ABPM) for 24 hours by oscillometric method Microlife WatchBP O3	Week 12
Coefficient of Variation of 24-hours, Diastolic Blood Pressure at Week 12	Blood pressure variability was evaluated with ambulatory blood pressure monitoring (ABPM) for 24 hours by oscillometric method Microlife WatchBP O3	Week 12
Coefficient of Variation Daytime, Systolic Blood Pressure at Week 12	Blood pressure variability was evaluated with ambulatory blood pressure monitoring (ABPM) from 8 a.m to 11 p.m. by oscillometric method Microlife WatchBP O3	Week 12
Coefficient of Variation Daytime, Diastolic Blood Pressure at Week 12	Blood pressure variability was evaluated with ambulatory blood pressure monitoring (ABPM) from 8 a.m. to 11 p.m. by oscillometric method Microlife WatchBP O3	Week 12
Coefficient of Variation Nighttime, Systolic Blood Pressure at Week 12	Blood pressure variability was evaluated with ambulatory blood pressure monitoring (ABPM) from 11 p.m. to 8 a.m. by oscillometric method Microlife WatchBP O3	Week 12
Coefficient of Variation Nighttime, Diastolic Blood Pressure at Week 12	Blood pressure variability was evaluated with ambulatory blood pressure monitoring (ABPM) from 11 p.m. to 8 a.m. by oscillometric method Microlife WatchBP O3	Week 12
Average Real Variability of Systolic Blood Pressure at Week 12	Blood pressure variability was evaluated with ambulatory blood pressure monitoring (ABPM) for 24 hours by oscillometric method Microlife WatchBP O3	Week 12
Average Real Variability of Diastolic Blood Pressure at Week 12	Blood pressure variability was evaluated with ambulatory blood pressure monitoring (ABPM) for 24 hours by oscillometric method Microlife WatchBP O3	Week 12
Number of Participants With a Nondipper Circadian Blood Pressure Pattern at Week 12	Blood pressure variability was evaluated with ambulatory blood pressure monitoring (ABPM) for 24 hours by oscillometric method Microlife WatchBP O3	Week 12
Number of Participants With a Dipper Circadian Blood Pressure Pattern at Week 12	Blood pressure variability was evaluated with ambulatory blood pressure monitoring (ABPM) for 24 hours by oscillometric method Microlife WatchBP O3	Week 12
Number of Participants With a Dipper Reverse Circadian Blood Pattern at Week 12	Blood pressure variability was evaluated with ambulatory blood pressure monitoring (ABPM) for 24 hours by oscillometric method Microlife WatchBP O3	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body Weight at Week 12	The body weight was measured with a bioimpedance balance	Week 12
Body Mass Index at Week 12	Body Mas Index was calculated with the Quetelet index formula	Week 12
Office Systolic Blood Pressure at Week 12	Blood pressure was measured using the Omron 907-E digital sphygmomanometer (Healthcare, Inc.)	Week 12
Office of Diastolic Blood Pressure at Week 12	Blood pressure was measured using the Omron 907-E digital sphygmomanometer (Healthcare, Inc.)	Week 12
Fasting Plasma Glucose Levels at Week 12	The fasting glucose levels was evaluated with enzymatic/colorimetric techniques	Week 12
2-hours Plasma Glucose After a Oral Glucose Tolerance Test at Week 12	2-hours plasma glucose after a oral glucose tolerance test (75 g of glucose load). Glucose was evaluated with enzymatic/ colorimetric technique	Week 12
Glycated Hemoglobin A1c (A1C) at Week 12	A1C was evaluated by Enzyme-Linked ImmunoSorbent Assay (ELISA)	Week 12
Daytime Mean Arterial Pressure at Week 12	The mean arterial pressure was evaluated with ambulatory blood pressure monitoring (ABPM) from 8 a.m. to 11 p.m. by oscillometric method Microlife WatchBP O3	Week 12
Nighttime Mean Arterial Pressure at Week 12	The Mean Arterial Pressure was evaluated with ambulatory blood pressure monitoring (ABPM) from 11 p.m. to 8 a.m. by oscillometric method Microlife WatchBP O3	Week 12
Daytime Hypertensive Load at Week 12	The hypertensive load was evaluated with ambulatory blood pressure monitoring (ABPM) from 8 a.m. to 11 p.m. by oscillometric method Microlife WatchBP O3	Week 12
Nocturnal Hypertensive Load at Week 12	The Hypertensive Load was evaluated with ambulatory blood pressure monitoring (ABPM) from 11 p.m. to a.m. by oscillometric method Microlife WatchBP O3	Week 12
Number of Participants With Prediabetes at Week 12	Prediabetes was diagnosed with the criteria of the American Diabetes Association.	Week 12
Number of Participants With Prehypertension at Week 12	Prehypertension was diagnosed with the criteria of the Eighth Joint National Committee.	Week 12
Number of Participants With Prediabetes Plus Prehypertension at Week 12	Criteria of the American Diabetes Association and Eighth Joint National Committee were used to diagnosed prediabetes and prehypertension.	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): March 30, 2016
• Primary Completion (Actual): March 30, 2018
• Study Completion (Actual): June 29, 2018

Study Registration Dates

• First Submitted: December 13, 2016
• First Submitted That Met QC Criteria: December 29, 2016
• First Posted (Estimate): December 30, 2016

Study Record Updates

• Last Update Posted (Actual): November 9, 2020
• Last Update Submitted That Met QC Criteria: October 16, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Prediabetes; Prehypertension; Variability of blood pressure; ABPM; Dapagliflozin; SGLT2
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hyperglycemia; Prehypertension; Prediabetic State; Glucose Intolerance; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin
• Other Study ID Numbers: DAPA-BP variability

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No