Diabetes Mellitus, Renal Insufficiency, Safety Issues
Conditions
Brief summary
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.
Interventions
DRUGEmpagliflozin
Empagliflozin tablets enclosed with red capsules (Capsugel AAEL) by Kragerø Tablettproduksjon AS for blinding purpose
OTHERPlacebo
Placebo tablets made by Kragerø Tablettproduksjon AS and enclosed with red capsules (Capsugel AAEL) for blinding purpose
Sponsors
Oslo University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Weighted mean glucose | 24 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Waist-hip-ratio | 24 weeks | Change from baseline in waist-hip-ratio |
| Blood pressure | 24 weeks | Change from baseline in blood pressure, including orthostatic blood pressure |
| Arterial stiffness | 24 weeks | 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 |
| Renal function | 24 weeks | 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 |
| Fasting plasma glucose | 24 weeks | Change from baseline in fasting plasma glucose |
| 2 hour glucose concentration | 24 weeks | Change from baseline in 2 hour glucose concentration after an oral glucose tolerance test |
| Glycated hemoglobin (HbA1c) | 24 weeks | Change from baseline in HbA1c |
| Body weight | 24 weeks | Change from baseline in body weight |
| Bone mineral density | 24 weeks | 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 |
| Body composition | 24 weeks | 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Urinary glucose excretion | 24 weeks | 24 hour urine sampling at baseline and after 24 weeks to analyse change in urinary glucose excretion |
| Incidence of abnormal trough levels of immunosuppressive drugs | 24 weeks | Trough levels of immunosuppressive drugs (tacrolimus); number of participants with abnormal laboratory values |
| Adverse event | 24 weeks | Recording of adverse events that are related to treatment |
Countries
Norway
Outcome results
None listed