Empagliflozin and Renal Oxygenation in Healthy Volunteers

NCT03093103 | Completed Phase 2 DMC

• 1 other identifier: 2016-00099
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Nephropathy

Keywords

empagliflozin; kidney; BOLD-MRI

Outcome Measures

Primary Outcomes (1)

• Renal oxygenation

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

  18 months

Secondary Outcomes (4)

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

  18 months

• Acute and chronic effects of empagliflozin on renal resistance indexes and renal volume after 4 weeks treatment

  18 months

• Effects of empagliflozin on 24h blood pressure mesaurements

  18 months

• Effect of body weight on the renal response to empagliflozin

  18 months

Study Arms (2)

empagliflozin 10mg

ACTIVE COMPARATOR

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

Drug: Empagliflozin 10 mg

Placebo

PLACEBO COMPARATOR

Placebo will be taken qd for 4 weeks.

Drug: Placebo

Interventions

Empagliflozin 10 mg DRUG

Prescription of empagliflozin 10 mg once a day Follow-up of renal parameters including BOLD MRI

Also known as: Jardiance

empagliflozin 10mg

Placebo DRUG

Prescription of a placebo once a day Follow-up of renal parameters including BOLD MRI

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre Hospitalier Universitaire Vaudois: lead

Study Sites (1)

Service de Néphrologie

Lausanne, Canton of Vaud, 1011, Switzerland

Location

Related Publications (4)

• 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.

  PMID: 35391843 DERIVED

• 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.

  PMID: 35387874 DERIVED

• 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.

  PMID: 32567439 DERIVED

• 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.

  PMID: 29802538 DERIVED

MeSH Terms

Conditions

Kidney Diseases

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Michel Burnier, Prof

  Service de Néphrologie CHUV

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Placebo and Empagliflozin pills
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Randomised placebo-controlled double blind trial

Study Record Dates

• First Submitted: March 16, 2017
• First Posted: March 28, 2017
• Study Start: March 16, 2017
• Primary Completion: December 30, 2018
• Study Completion: December 31, 2018
• Last Updated: July 30, 2019

Record last verified: 2019-07

Locations

CH (1)