New Onset Diabetes Mellitus After Renal Transplantation
Conditions
Keywords
NODAT, kidney transplantation, beta cell function, insulin, Tacrolimus, Cyclosporine A
Brief summary
New onset diabetes after transplantation (NODAT) is a frequent and feared complication after kidney transplantation and leads to an increase in cardiovascular complications as well as in the rate of graft loss. Very little data exist on how patients in which NODAT has been diagnosed should be treated. It is suspected that Cylosporine A (Sandimmun, TM) is less diabetogenic than Tacrolimus (Prograf, TM). Furthermore, it has been described that early initiation of insulin treatment in Diabetes mellitus type 2 can preserve and improve the function of the insulin secreting cells in the pancreas. Therefore, the investigators test the effects of conversion from Tacrolimus to Cyclosporine A in patients with newly diagnosed NODAT who have just started early treatment with insulin. The hypothesis is that patients who are treated with insulin and who are switched to Cyclosporine A have improved glucose metabolism compared to patients who are treated with insulin and who remain on Tacrolimus therapy.
Interventions
DRUGCyclosporine A
Patients randomized into arm A will be switched from Tacrolimus to Cyclosporine A. Conversion will be done by a stop and go protocol. Patients will take their last dose Tacrolimus in the morning of the day of conversion and will start taking Cyclosporine A in the evening of the same day at a dose of 3mg/kg/d. The first measurement of Cyclosporine A trough levels will be performed 3 days after conversion and the dose will then be adjusted if necessary. Furthermore, treatment with NPH insulin once daily in the morning will be initiated.
DRUGTacrolimus
Patients in arm B will remain on their immunosuppressive therapy with Tacrolimus. Furthermore, treatment with NPH insulin once daily in the morning will be initiated.
Sponsors
Medical University of Vienna
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Newly diagnosed NODAT defined by pathologic OGTT (2h, 75mg glucose): glucose ≥ 200mg/dl * Defect in insulin secretion as judged by OGTT and HOMA B * Renal transplantation (deceased or living donor) and treatment with the standard immunosuppression at our center, consisting of tacrolimus, mycophenolate mofetil, prednisone triple therapy without any induction * stable graft function for more than 3 months post transplant * informed consent of the patient
Exclusion criteria
* patients with prior history of type 1 or type 2 diabetes * time since transplantation more than 20 years * allergy against long-acting insulin or cyclosporine A * body mass index (BMI) \> 35 * pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 90 days OGTT | 90 days | The primary endpoint will be the difference in the 2h glucose value obtained from an oral glucose tolerance test (OGTT) after 90 days compared to baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Beta cell function | 90 and 180 days | One secondary endpoint is the change in beta cell function after 90 days compared to baseline as determined by a frequent sampling oral glucose glucose tolerance test. |
| Graft rejection | whole study period | The rate of episodes of acute allograft rejection will be compared between the two treatment arms. |
| Hypoglycemia | whole study period | The rate of clinically relevant hypoglycemic episodes will be desribed. |
Countries
Austria
Outcome results
None listed