EMPRA (EMPagliflozin and RAs in Kidney Disease)

Summary

This study will be a prospective, clinical pilot study in CKD patients to show whether Empagliflozin in addition to ACEi treatment significantly increases Ang 1-7 levels compared to ACEi treatment alone.

Null and alternative hypotheses:

H0: Empagliflozin in addition to ACEi treatment does not increase Ang 1-7 levels more than ACEi treatment alone.

H1: Empagliflozin in addition to ACEi treatment significantly increases Ang 1-7 levels compared to ACEi treatment alone

Methodology:

Two groups of 24 chronic kidney disease (CKD) patients, respectively, with and without type 2 diabetes will be randomized into the study medication or placebo group. The number of patients per treatment arms is n = 12. Included and consented patients will be subjected to an initial 2-week run-in period for conversion of current RAS blocking medications to ACEi therapy with enalapril or ramipril and respective dose titration to 10 mg enalapril 2 x daily and 10 mg ramipril 1 x daily. Additional antihypertensive medication will be standardized as feasible, with the primary goal of keeping blood pressure as recommended by KDIGO. Following the 2-week run-in phase, all study patients will be subjected to blood collection including the first RAS quantification (RAS Fingerprint) and assessment of HDL composition, as well as urinary analysis and bioimpedance fluid status assessment (BCM measurement). Subsequently, patients will be randomized to either receive empagliflozin (at a dose of 10 mg daily) or placebo. Subsequently, biweekly study visits including electrolyte and glucose (plasma and urine) monitoring as well as BCM measurement will take place. After 12 weeks of study medication intake, a concluding study visit will be scheduled for final RAS quantification (RAS Fingerprint) and HDL analyses as well as final blood and urinary analysis and BCM measurement. Initially, blood and urine will be collected at the clinical visit as part of the routine blood obtainment (no additional effort on patients). From these routine measurements we will be able to extract information regarding the patient's current CKD stage as well as other relevant laboratory parameters (e.g. HbA1c, UACR, etc.). Furthermore, we will document the patient's current medication and significant comorbidities.

Primary analysis variable/endpoint:

The difference of Ang 1-7 increase from baseline between a 3-month treatment with empagliflozin on top of ACEi treatment compared to ACEi treatment alone

Most important secondary analysis variables/endpoints:

1. Simultaneous quantitative changes of multiple RAS effector angiotensin levels determined by mass-spectrometry
2. Recurrence of Ang II levels determined by mass-spectrometry
3. HDL parameters (protein composition of HDL)
4. Renal parameters (albuminuria reduction measured by urinary albumin-creatinine ratio (UACR), renal function (estimated glomerular filtration rate (GFR), serum-creatinine)
5. Urinary electrolyte levels
6. Urinary glucose levels
7. Urinary RAS metabolites (angiotensinogen, ACE and ACE2 levels, ACE2 activity)
8. Blood pressure determined by ambulatory blood pressure measurements
9. Body volume determined by bioimpedance fluid status assessment (BCM measurement)
10. OCR and ECAR in PBMCs determined by Seahorse Flux Analyzer
11. Assessment of reduction of salt sensitivity by using salt sensitivity test with empagliflozin

Conditions

• Diabetic Kidney Disease
• Diabetes Mellitus, Type 2
• Chronic Kidney Disease stage3
• Chronic Kidney Disease stage4

Interventions

DRUG

Empagliflozin 10 MG [Jardiance]

administered orally once daily

DRUG

Placebo Oral Tablet

administered orally once daily

Sponsors & Collaborators

• Attoquant Diagnostics

  collaborator UNKNOWN

• Medical University of Vienna

  lead OTHER

Principal Investigators

• Manfred Hecking, MD · Department of Internal Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Austria

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2017-04-15

Primary Completion

2019-06-18

Completion

2019-08-07

Countries

• Austria

Study Locations