MedPath

Empagliflozin and Renal Oxygenation in Healthy Volunteers

Phase 2
Completed
Conditions
Nephropathy
Interventions
Registration Number
NCT03093103
Lead Sponsor
Centre Hospitalier Universitaire Vaudois
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
45
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboPlacebo will be taken qd for 4 weeks.
empagliflozin 10mgEmpagliflozin 10 mgEmpagliflozin (Jardiance) 10mg is an SGLT-2inhibitor. The drug will be taken qd for 4 weeks.
Primary Outcome Measures
NameTimeMethod
Renal oxygenation18 months

The acute and chronic effect of empagliflozin on renal oxygenation will be assessed by BOLD-MRI

Secondary Outcome Measures
NameTimeMethod
Acute and chronic effects of empagliflozin on renal resistance indexes and renal volume after 4 weeks treatment18 months

Will be assessed by renal ultrasound

Effect of body weight on the renal response to empagliflozin18 months

Different groups of BMI will be evaluated

Acute and chronic effects of empagliflozin on diurnal and nocturnal sodium, potassium, uric acid, calcium, phosphate, glucose and lithium clearances after 4 weeks treatment18 months

Will be assessed on 24h urinary collections

Effects of empagliflozin on 24h blood pressure mesaurements18 months

WIll be assessed by ambulatory blood pressure measurements

Trial Locations

Locations (1)

Service de Néphrologie

🇨🇭

Lausanne, Vaud, Switzerland

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