Clinical trial NCT03093103: Empagliflozin and Renal Oxygenation in Healthy Volunteers
Official title: Effects of the SGLT2 Inhibitor Empagliflozin on Renal Tissue Oxygenation in Non-diabetic Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Nephropathy
Keywords: empagliflozin
kidney
BOLD-MRI
Lead sponsor: Centre Hospitalier Universitaire Vaudois
Sponsor class: OTHER
First posted: 2017-03-28
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomised placebo-controlled double blind trial
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Renal oxygenation
timeFrame: 18 months
Secondary outcomes:
measure: Acute and chronic effects of empagliflozin on diurnal and nocturnal sodium, potassium, uric acid, calcium, phosphate, glucose and lithium clearances after 4 weeks treatment
timeFrame: 18 months
measure: Acute and chronic effects of empagliflozin on renal resistance indexes and renal volume after 4 weeks treatment
timeFrame: 18 months
measure: Effects of empagliflozin on 24h blood pressure mesaurements
timeFrame: 18 months
measure: Effect of body weight on the renal response to empagliflozin
timeFrame: 18 months
Other outcomes:
Locations:
city: Lausanne
country: Switzerland
facility: Service de Néphrologie
state: Vaud
Study officials:
affiliation: Service de Néphrologie CHUV
name: Michel Burnier, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zanchi A, Pruijm M, Muller ME, Ghajarzadeh-Wurzner A, Maillard M, Dufour N, Bonny O, Wuerzner G, Burnier M. Twenty-Four Hour Blood Pressure Response to Empagliflozin and Its Determinants in Normotensive Non-diabetic Subjects. Front Cardiovasc Med. 2022 Mar 22;9:854230. doi: 10.3389/fcvm.2022.854230. eCollection 2022.
citation: Harmacek D, Pruijm M, Burnier M, Muller ME, Ghajarzadeh-Wurzner A, Bonny O, Zanchi A. Empagliflozin Changes Urine Supersaturation by Decreasing pH and Increasing Citrate. J Am Soc Nephrol. 2022 Jun;33(6):1073-1075. doi: 10.1681/ASN.2021111515. Epub 2022 Apr 6.
citation: Zanchi A, Burnier M, Muller ME, Ghajarzadeh-Wurzner A, Maillard M, Loncle N, Milani B, Dufour N, Bonny O, Pruijm M. Acute and Chronic Effects of SGLT2 Inhibitor Empagliflozin on Renal Oxygenation and Blood Pressure Control in Nondiabetic Normotensive Subjects: A Randomized, Placebo-Controlled Trial. J Am Heart Assoc. 2020 Jul 7;9(13):e016173. doi: 10.1161/JAHA.119.016173. Epub 2020 Jun 20.
citation: Muller ME, Pruijm M, Bonny O, Burnier M, Zanchi A. Effects of the SGLT-2 Inhibitor Empagliflozin on Renal Tissue Oxygenation in Non-Diabetic Subjects: A Randomized, Double-Blind, Placebo-Controlled Study Protocol. Adv Ther. 2018 Jun;35(6):875-885. doi: 10.1007/s12325-018-0708-y. Epub 2018 May 25.