Improving Secretion of Insulin in New Onset Diabetes After Renal Transplantation

New Onset Diabetes Mellitus After Renal Transplantation Clinical Trial

— ISINODAT  

Official title:

A Randomized, Prospective Trial to Evaluate the Effect of Conversion From Tacrolimus to Cyclosporine A After Early Initiation of Insulin Therapy in Patients With New-onset Diabetes Mellitus After Kidney Transplantation

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01268995
• Other study ID #: EudraCT: 2009-012712-40
• Status: Terminated
• Phase: Phase 2
• First received: January 3, 2011
• Last updated: January 3, 2011
• Start date: September 2009
• Est. completion date: December 2010

Study information

• Verified date: January 2011
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Austrian Medicines and Medical Devices Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 32
• Est. completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• New Onset Diabetes Mellitus After Renal Transplantation

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
Austria	Medical University of Vienna/General Hospital	Vienna

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Vienna

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	90 days OGTT	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.	90 days	No
Secondary	Beta cell function	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.	90 and 180 days	No
Secondary	Graft rejection	The rate of episodes of acute allograft rejection will be compared between the two treatment arms.	whole study period	Yes
Secondary	Hypoglycemia	The rate of clinically relevant hypoglycemic episodes will be desribed.	whole study period	Yes