Acute Effects of SGLT2 Inhibitor on Kidney Allograft Oxygen Tension (SGL-TX-MR)

Acute Effects of SGLT2 Inhibitor on Kidney Allograft Oxygen Tension: A Randomized, Double-blind, Placebo Controlled Crossover Trial

The goal of this clinical trial is to investigate if a single dose of oral SGLT2i, (50 mg Jardiance) will change oxygen tension in the kidney transplant.

The main questions it aims to answer are:

• Does a single dose of oral SGLT2i (50 mg Jardiance) change oxygen tension in the kidney transplant cortex and medulla, estimated by magnetic resonance imaging?
• Does a single dose of oral SGLT2i (50 mg Jardiance) change kidney transplant cortical and medullary perfusion?
• Does a single dose of oral SGLT2i (50 mg Jardiance) change kidney transplant artery blood flow?
• Does a single dose of oral SGLT2i (50 mg Jardiance) change blood glucoses, blood pressure and heart rate?

Researchers will compare a single dose of oral SGLT2i (50 mg Jardiance) to a placebo (a look-alike substance that contains no drug) to see if a single dose of oral SGLT2i (50 mg Jardiance) changes oxygen tension in the kidney transplant.

Kidney transplant recipients with out diabetes will:

• Meet for two intervention days.
• A single dose of oral SGLT2i (50 mg Jardiance) or placebo will be given in random order, separated by at least 2 week washout period, the experiment will be repeated with the opposite treatment.
• Kidney cortex oxygenation, and blood flow in different compartments of the kidney transplant, is estimated by blood-oxygen-dependent level magnetic resonance imaging (BOLD-MRI). Patients are evaluated by routine clinical examination and routine biochemical measures for kidney transplant patients.

Study Overview

• Status: Active, not recruiting
• Conditions: Randomized Controlled Trial; Magnetic Resonance Imaging (MRI); Sodium-Glucose Transporter 2 Inhibitors; Kidney Transplantation Recipients; Placebo Control Design; Non-Diabetic Patients
• Intervention / Treatment: Drug: JARDIANCE 25mg; Drug: Placebo

Detailed Description

Background:

Kidney transplantation is the best treatment of end-stage renal disease (ESRD), although median allograft survival is only 15 years. In non-transplant diabetic and non-diabetic patient's sodium-glucose co-transporter type 2 inhibitors (SGLT2i) protect kidney function, possibly by reducing the proximal tubule transport workload with subsequent improvement of renal oxygenation and relieve hypoxia.

Hypothesis:

SGLT2i in kidney transplant recipients (KTR) will improve kidney allograft cortex oxygenation.

Research Objective:

We aim to test the acute effect of SGLT2i on kidney allograft oxygen tension.

Design:

A randomized, double-blind, placebo-controlled, crossover intervention study. Designed according to the CONSORT statement

Methods:

A single dose of oral SGLT2i (50 mg Jardiance) and placebo in random order, separated by at least 2 week washout period, the experiment will be repeated with the opposite treatment.

Kidney cortex oxygenation and blood flow in different compartments of the kidney allograft will be estimated by blood-oxygen-dependent level magnetic resonance imaging (BOLD-MRI). Patients will be evaluated by routine clinical examination and routine biochemical measures for transplant patients.

Primary endpoint:

- Kidney allograft cortical and medullary oxygen tension, estimated by BOLD-MRI based renal T2* relaxation rate.

Secondary endpoint:

• Renal cortical and medullary perfusion ml/100 g/min
• Renal artery blood flow ml/min
• Blood glucose mmol/L
• Systolic blood pressure (SysBP) and diastolic blood pressure (DiaBP) mmHg
• Heart rate (HR), beats min-1

Study population:

8 Non-diabetic kidney transplant recipients > 6 months post-transplant and stable eGFR >20 ml/min will be recruited from Odense University Hospital (OUH) kidney transplant outpatient clinic.

• Study Type: Interventional
• Enrollment (Estimated): 8
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Odense C, Denmark, 5000
    • Department of Nephrology, Odense University Hospital Kløvervænget 6, Enterance 93, 3. floor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female patients, age ≥ 18 years.
• Non-diabetic kidney transplant recipients
• > 6 months post-transplant
• Stable eGFR> 20 ml/min (defined as eGFR 20 ml/min ± 5 ml/min variation in the last 3 months)
• Immunosuppressive: Tacrolimus (Adport) and Mycophenolatmofetil (Myfenax/Cellcept/Mycophenolatmofetil)
• Capable of lying in a MR-scanner

• Capable of providing a signed informed consent and comply with study requirements.

  • Negativ pregnancy test

Exclusion Criteria:

• Diabetic kidney disease type 1 or 2 (World Health Organization (WHO) criteria)

  • Hemoglobin A1c ≥ 48 mmol/mol
  • Fasting venous plasma glucose ≥ 7,0 mmol/l or
  • 2-hours venous plasma glucose ≥ 11,1 mmol/l after oral glucose tolerance test (OGTT).
• Renal allograft failure (eGFR< 20 ml/min)
• Alanine aminotransferase (ALAT) > 3 x upper normal limit
• Bilirubin > 2 x upper normal limit
• Prednisone treatment
• Pregnancy
• Breastfeeding
• Exclusion criteria for MRI o Claustrophobia/physical not able to lie in MR-s

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: SGLT2i; Single dose of SGLT2i (Jardiance 50 mg)	Drug: JARDIANCE 25mg; The intervention will be SGLT2i compared with placebo. The trial include a total of 8 non-diabetic kidney transplant recipients. 4 patients will randomly be assigned to start in the active arm, and treated with a single dose SGLT2i at intervention day 1 and a single dose placebo at intervention day 2. 4 patients will randomly be assigned to start in the non-active arm, each participant will be treated with a single dose placebo at intervention day 1 and a single dose SGLT2i at intervention day 2.; Other Names: SGLT2i
Placebo Comparator: Placebo; Single dose placebo	Drug: Placebo; The intervention will be SGLT2i compared with placebo. The trial include a total of 8 non-diabetic kidney transplant recipients. 4 patients will randomly be assigned to start in the active arm, and treated with a single dose SGLT2i at intervention day 1 and a single dose placebo at intervention day 2. 4 patients will randomly be assigned to start in the non-active arm, each participant will be treated with a single dose placebo at intervention day 1 and a single dose SGLT2i at intervention day 2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kidney allograft cortex oxygenation, T2*	BOLD-MRI, T2* cortex, s-1	T2* measured at baseline, 3 and 6 hours post-intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal cortical perfusion, (ml/100g/min)	BOLD-MRI estimated renal cortical perfusion, (ml/100 g/min)	Renal cortical perfusion, measured at baseline, 3 and 6 hours post-intervention

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal allograft artery blood flow (ml/min)	BOLD-MRI, renal allograft artery blood flow (ml/min)	Renal allograft artery blood flow measured at baseline, 3 and 6 hours post-intervention
Blood glucose (mmol/L)	Blood glucose (mmol/L), estimated by handheld blood glucose meter	Blood glucose, measured at baseline, 3 and 6 hours post-intervention
Blood pressure	Systolic and diastolic blood pressure (mmHg), Estimated by a validated blood pressure device.	Bloodpressure measured at baseline, 3 and 6 hours post-intervention

Collaborators and Investigators

• Sponsor: Odense University Hospital
• Investigators: Principal Investigator: Lotte B Lange, MD, Department of Nephrology, Odense University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2025
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: April 1, 2025
• First Submitted That Met QC Criteria: April 15, 2025
• First Posted (Actual): April 18, 2025

Study Record Updates

• Last Update Posted (Actual): July 31, 2025
• Last Update Submitted That Met QC Criteria: July 30, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: MRI; RCT; Kidney Transplant; SGLT2i; BOLD-MRI; Magnetic resonance Imaging; Kidney Transplant Recipients; Blood oxygen level dependent MRI; non-diabetic patients; Sodium-glucose Transporter 2 inhibitors
• Additional Relevant MeSH Terms: Sodium-Glucose Transporter 2 Inhibitors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Empagliflozin
• Other Study ID Numbers: EU CT:2024-513765-40-00

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Data Sharing Statement:

Data Available:

Individual participant data (IPD) that underlie the results reported in the published article will be shared after de-identification. This includes text, tables, figures, and appendices.

Supporting Documents:

The study protocol and statistical analysis plan will also be made available.

Time Frame:

Data will be shared immediately following publication. There is no specified end date for availability.

Criteria for Access:

Data will be shared with researchers who submit a methodologically sound proposal aimed at achieving the goals outlined in their approved research proposal.

Access Mechanism:

Interested researchers should direct their proposals to: lotte.borg.lange@rsyd.dk.

To gain access, requestors will be required to sign a data access agreement.

Data Storage:

The data will be stored for 25 years on a secure third-party platform (OPEN).

IPD Sharing Time Frame

The data will be available after the last patients last visit, which is estimated for summer 2025

Data Storage:

The data will be stored for 25 years on a secure third-party platform (OPEN).

IPD Sharing Access Criteria

Criteria for Access:

Data will be shared with researchers who submit a methodologically sound proposal aimed at achieving the goals outlined in their approved research proposal.

Access Mechanism:

Interested researchers should direct their proposals to: lotte.borg.lange@rsyd.dk.

To gain access, requestors will be required to sign a data access agreement.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No