Effect of Dapagliflozin on Blood Pressure Variability in Prediabetes and Prehypertension

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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PreDiabetes, Prehypertension

Intervention / Treatment
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* Drug: Dapagliflozin
* Drug: Placebo - Cap


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 60 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: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ABPM, Prediabetes, Prehypertension, Variability of blood pressure, Dapagliflozin, SGLT2