Empagliflozin and Renal Oxygenation in Healthy Volunteers (EMPA-REIN)

Vaud University Hospital Center

Status and phase: Completed; Phase 2

Conditions: Nephropathy

Treatments: Drug: Placebo; Drug: Empagliflozin 10 mg

Study type: Interventional

Funder types: Other

Identifiers

NCT03093103

2016-00099

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 45 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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45 participants in 2 patient groups, including a placebo group

empagliflozin 10mg

Active Comparator group

Description:

Empagliflozin (Jardiance) 10mg is an SGLT-2inhibitor. The drug will be taken qd for 4 weeks.

Treatment:

Drug: Empagliflozin 10 mg

Placebo

Placebo Comparator group

Description:

Placebo will be taken qd for 4 weeks.

Treatment:

Drug: Placebo