Empagliflozin and Renal Oxygenation in Healthy Volunteers

Study Overview
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Brief Summary
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SGLT-2 inhibitors belong to a new class of hypoglycemic drugs with the unique property of decreasing blood glucose through an increase in glucosuria. These drugs inhibit the sodium glucose transporter 2 (SGLT2) expressed at the luminal membrane of the proximal tubule. SGLT-2 inhibition in type 2 diabetic subjects and in healthy volunteers shifts the threshold for renal glucose excretion to lower levels. This effect is independent from insulin. The inhibition of SGLT2 decreases HbA1C, systolic blood pressure and weight in diabetic subjects. Recently, the EMPA-REG trial demonstrated a decrease in cardiovascular mortality and renal endpoints in empagliflozin treated type 2 diabetic patients with established cardio-vascular disease. Because this novel hypoglycemic drug has unique and direct effects on renal tissue metabolism, it is important to better examine its effects on the kidney. With this study, we propose to explore the effects of empagliflozin on renal tissue oxygenation. Our hypothesis is that SGLT-2 inhibition decreases renal cortical energy requirements with consequently an increase in renal tissue oxygenation.

Detailed Description
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This study is a double-blind, randomized, placebo-controlled study that will examine the acute and chronic renal effects of empagliflozin in healthy volunteers. A total of 45 healthy volunteers will be included in the study: 15 normal weight, 15 overweight (BMI: 25-30kg/m2) and 15 obese (BMI>30kg/m2) non diabetic subjects (as determined after an oral glucose tolerance test). Empagliflozin 10mg vs placebo will be administered in a blinded fashion qd. The acute and chronic renal response to empagliflozin will be assessed.

Official Title
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Effects of the SGLT2 Inhibitor Empagliflozin on Renal Tissue Oxygenation in Non-diabetic Subjects

Conditions
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Nephropathy

Intervention / Treatment
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* Drug: Empagliflozin 10 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Normal weight (BMI: 19-24.9kg/m2), overweight (BMI:25-30kg/m2) or obesity (BMI>30kg/m2) Men and women (with a negative pregnancy test) during the follicular phase of the menstrual cycle. All groups will have a balanced number of men and women. OGTT/HbA1C: normal or pre-diabetes eGFR>60ml/min, albumin/creatinine ratio <3.3mg/mmol (<30 mg/g) Signed consent form Normal renal ultrasound Normal urine dipstick Exclusion Criteria: Antihypertensive therapy NSAID treatment Former bariatric surgery Age<18y or >50y At risk of dehydration or hypotension Past history of recurrent genital or urinary tract infections Contra-indication for MR imaging (pacemaker or other implanted metallic device, claustrophobia) Pregnancy Sustained systolic blood pressure >150mmHg or diastolic blood pressure >95mmHg

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomised placebo-controlled double blind trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: empagliflozin 10mg<br>Empagliflozin (Jardiance) 10mg is an SGLT-2inhibitor. The drug will be taken qd for 4 weeks. | Drug: Empagliflozin 10 mg<br>* Prescription of empagliflozin 10 mg once a day Follow-up of renal parameters including BOLD MRI<br>* Other names: Jardiance;|
| Placebo Comparator: Placebo<br>Placebo will be taken qd for 4 weeks. | Drug: Placebo<br>* Prescription of a placebo once a day Follow-up of renal parameters including BOLD MRI<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal oxygenation | The acute and chronic effect of empagliflozin on renal oxygenation will be assessed by BOLD-MRI | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute and chronic effects of empagliflozin on diurnal and nocturnal sodium, potassium, uric acid, calcium, phosphate, glucose and lithium clearances after 4 weeks treatment | Will be assessed on 24h urinary collections | 18 months | 
| Acute and chronic effects of empagliflozin on renal resistance indexes and renal volume after 4 weeks treatment | Will be assessed by renal ultrasound | 18 months | 
| Effects of empagliflozin on 24h blood pressure mesaurements | WIll be assessed by ambulatory blood pressure measurements | 18 months | 
| Effect of body weight on the renal response to empagliflozin | Different groups of BMI will be evaluated | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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kidney, empagliflozin, BOLD-MRI