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

Odense University Hospital

Status and phase: Active, not recruiting; Phase 4

Conditions: Sodium-Glucose Transporter 2 Inhibitors; Placebo Control Design; Magnetic Resonance Imaging (MRI); Randomized Controlled Trial; Non-Diabetic Patients; Kidney Transplantation Recipients

Treatments: Drug: JARDIANCE 25mg; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT06933355

EU CT:2024-513765-40-00

Details and patient eligibility

About

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.

Full 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.

Enrollment: 8 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

---

8 participants in 2 patient groups, including a placebo group

SGLT2i

Active Comparator group

Description:

Single dose of SGLT2i (Jardiance 50 mg)

Treatment:

Drug: JARDIANCE 25mg

Placebo

Placebo Comparator group

Description:

Single dose placebo

Treatment:

Drug: Placebo