Empagliflozin in Renal Transplant Recipients (EMPA-RenalTx)

Efficacy and Safety of Empagliflozin in Renal Transplant Recipients With Post-transplantation Diabetes Mellitus

This is a single-center, prospective, controlled, double-blind, randomized study. A total of 50 renal transplant recipients diagnosed with post-transplantation diabetes mellitus (PTDM) will be included more than 1 year after transplantation and randomized 1:1 to empagliflozin (Jardiance®) 10 mg or placebo once daily for 24 weeks. Patients with estimated glomerular filtration rate below 30 mL/min will be excluded. Oral glucose tolerance test, 72h continuous glucose monitoring (iPro™2), measurement of arterial stiffness, body composition (including visceral fat), 24h blood pressure and 24h urinary glucose excretion will be performed at baseline and after 24 weeks in addition to standard safety measurements. Two safety visits will be performed at week 8 and 16. All concomitant medication, diet and exercise will be kept stable during the study period. The objective of the present study is to answer whether empagliflozin safely and effectively improves glucose metabolism together with weight loss in renal transplant recipients with PTDM.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus; Renal Insufficiency; Safety Issues
• Intervention / Treatment: Drug: Empagliflozin; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 4

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway, 0424
    • Oslo University Hospital Rikshospitalet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Renal transplant recipient transplanted more than 1 year ago
• Stable renal function (<20% deviation in serum creatinine within last 2 months)
• Stable immunosuppressive therapy ≥3 months before inclusion
• Diagnosed with PTDM:

(fasting plasma glucose ≥7.0 mmol/l and/or 2-hour plasma glucose ≥11.1 mmol/l following an oral glucose tolerance test)

-Signed informed consent and expected cooperation of the patients

Exclusion Criteria:

• Estimated GFR <30 ml/min/1.73 m2
• Pregnant or nursing mothers
• Hypersensitivity to the active substance (IMP) or to any of the excipients
• Any reason why, in the opinion of the investigator, the patient should not participate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Empagliflozin; 10 mg once daily for 24 weeks	Drug: Empagliflozin; Empagliflozin tablets enclosed with red capsules (Capsugel AAEL) by Kragerø Tablettproduksjon AS for blinding purpose; Other Names: Jardiance
Placebo Comparator: Placebo; 1 capsule once daily for 24 weeks	Other: Placebo; Placebo tablets made by Kragerø Tablettproduksjon AS and enclosed with red capsules (Capsugel AAEL) for blinding purpose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weighted mean glucose	The primary endpoint will be change from baseline in weighted mean glucose at week 24 compared to placebo. Each patient will perform continuous plasma glucose monitoring (CGM, iProTM2) for 72 hours at baseline and after 24 weeks.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting plasma glucose	Change from baseline in fasting plasma glucose	24 weeks
Glycated hemoglobin (HbA1c)	Change from baseline in HbA1c	24 weeks
2 hour glucose concentration	Change from baseline in 2 hour glucose concentration after an oral glucose tolerance test	24 weeks
Body weight	Change from baseline in body weight	24 weeks
Waist-hip-ratio	Change from baseline in waist-hip-ratio	24 weeks
Bone mineral density	Measurement of bone mineral density, using low dosage radiation (dual-energy X-ray absorptiometry (DEXA) scan) to assess the amount (grams) of mineral that are packed into a segment of bone	24 weeks
Body composition	Body composition (visceral fat, metabolic measurement) will be determined using the software CoreScan (encore version 14.10, GE Healthcare) on the DEXA scans. This will allow us to analyze changes in body fat compartments to explain overall weight reduction	24 weeks
Blood pressure	Change from baseline in blood pressure, including orthostatic blood pressure	24 weeks
Arterial stiffness	Pulse wave velocity, using a SphygmoCor device, measuring arterial stiffness will be performed in addition to pulse wave analysis evaluating the shape and amplitude of the aortic pulse wave	24 weeks
Renal function	Renal function, defined as glomerular filtration rate (GFR), will be evaluated by creatinine and cystatin C-based estimated GFR using the chronic kidney disease epidemiology collaboration (CKD-EPI) formula. Fasting plasma creatinine and Cystatin C will be drawn at the same time and analyses will be performed at the Hospital central laboratory	24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of abnormal trough levels of immunosuppressive drugs	Trough levels of immunosuppressive drugs (tacrolimus); number of participants with abnormal laboratory values	24 weeks
Adverse event	Recording of adverse events that are related to treatment	24 weeks
Urinary glucose excretion	24 hour urine sampling at baseline and after 24 weeks to analyse change in urinary glucose excretion	24 weeks

Collaborators and Investigators

• Sponsor: Oslo University Hospital

Publications and helpful links

General Publications

• Lo C, Toyama T, Oshima M, Jun M, Chin KL, Hawley CM, Zoungas S. Glucose-lowering agents for treating pre-existing and new-onset diabetes in kidney transplant recipients. Cochrane Database Syst Rev. 2020 Jul 30;8(8):CD009966. doi: 10.1002/14651858.CD009966.pub3.
• Halden TAS, Kvitne KE, Midtvedt K, Rajakumar L, Robertsen I, Brox J, Bollerslev J, Hartmann A, Asberg A, Jenssen T. Efficacy and Safety of Empagliflozin in Renal Transplant Recipients With Posttransplant Diabetes Mellitus. Diabetes Care. 2019 Jun;42(6):1067-1074. doi: 10.2337/dc19-0093. Epub 2019 Mar 12.

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2016
• Primary Completion (Actual): June 28, 2018
• Study Completion (Actual): June 28, 2018

Study Registration Dates

• First Submitted: March 15, 2017
• First Submitted That Met QC Criteria: May 15, 2017
• First Posted (Actual): May 17, 2017

Study Record Updates

• Last Update Posted (Actual): March 15, 2019
• Last Update Submitted That Met QC Criteria: March 13, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Kidney Diseases; Urologic Diseases; Endocrine System Diseases; Diabetes Mellitus; Renal Insufficiency; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Empagliflozin
• Other Study ID Numbers: 2016/911; 2016-001705-17 (EudraCT Number); 2016069 (Other Grant/Funding Number: South-Eastern Norway Regional Health Authority)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No