Improving Secretion of Insulin in New Onset Diabetes After Renal Transplantation

NCT ID: NCT01268995

Last Updated: 2011-01-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-30
• Study Completion Date: 2010-12-31

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.

Conditions

New Onset Diabetes Mellitus After Renal Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cyclosporine A

Patients in this arm will be switched from immunosuppressive therapy with Tacrolimus to Cyclosporine A. Furthermore, patients in this arm will commence insulin treatment with NPH-insulin to reach normoglycemia. After the achievement of normoglycemia the insulin treatment will be continued for three more weeks and than terminated.

Group Type: EXPERIMENTAL

Cyclosporine A

Intervention Type: DRUG

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.

Tacrolimus

Patients in this arm will remain on their immunosuppressive therapy with Tacrolimus. Furthermore, patients in this arm will commence insulin treatment with NPH-insulin to reach normoglycemia. After the achievement of normoglycemia the insulin treatment will be continued for three more weeks and than terminated.

Group Type: ACTIVE_COMPARATOR

Tacrolimus

Intervention Type: DRUG

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.

Interventions

Cyclosporine 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.

Intervention Type: DRUG

Tacrolimus

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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical University of Vienna

OTHER

Sponsor Role: lead

Responsible Party

Medical University of Vienna

Locations

Medical University of Vienna/General Hospital

Vienna, , Austria

Countries

Austria

Other Identifiers

EudraCT: 2009-012712-40

Identifier Type: -

Identifier Source: org_study_id