Empagliflozin and Renal Oxygenation in Healthy Volunteers

Nephropathy Clinical Trial

— EMPA-REIN  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03093103
• Other study ID #: 2016-00099
• Status: Completed
• Phase: Phase 2
• Start date: March 16, 2017
• Est. completion date: December 31, 2018

Study information

• Verified date: July 2019
• Source: Centre Hospitalier Universitaire Vaudois
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: December 31, 2018
• Est. primary completion date: December 30, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Nephropathy

Intervention

Drug:
• Empagliflozin 10 mg
Prescription of empagliflozin 10 mg once a day Follow-up of renal parameters including BOLD MRI
• Placebo
Prescription of a placebo once a day Follow-up of renal parameters including BOLD MRI

Locations

Country	Name	City	State
Switzerland	Service de Néphrologie	Lausanne	Vaud

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire Vaudois

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Renal oxygenation	The acute and chronic effect of empagliflozin on renal oxygenation will be assessed by BOLD-MRI	18 months
Secondary	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
Secondary	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
Secondary	Effects of empagliflozin on 24h blood pressure mesaurements	WIll be assessed by ambulatory blood pressure measurements	18 months
Secondary	Effect of body weight on the renal response to empagliflozin	Different groups of BMI will be evaluated	18 months