Improving Secretion of Insulin in New Onset Diabetes After Renal Transplantation - Full Text View

Purpose

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.

Condition	Intervention	Phase
New Onset Diabetes Mellitus After Renal Transplantation	Drug: Cyclosporine A Drug: Tacrolimus	Phase 2

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

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Diabetes Medicines Kidney Transplantation

Drug Information available for: Insulin, NPH Insulin human Cyclosporine Tacrolimus

U.S. FDA Resources

Further study details as provided by Medical University of Vienna:

Primary Outcome Measures:

90 days OGTT [ Time Frame: 90 days ] [ Designated as safety issue: No ]
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 Outcome Measures:

Beta cell function [ Time Frame: 90 and 180 days ] [ Designated as safety issue: No ]
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 [ Time Frame: whole study period ] [ Designated as safety issue: Yes ]
The rate of episodes of acute allograft rejection will be compared between the two treatment arms.
Hypoglycemia [ Time Frame: whole study period ] [ Designated as safety issue: Yes ]
The rate of clinically relevant hypoglycemic episodes will be desribed.

Estimated Enrollment:	32
Study Start Date:	September 2009
Study Completion Date:	December 2010

Arms	Assigned Interventions
Experimental: 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.	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.
Active Comparator: 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.	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.

Arms

Assigned Interventions

Experimental: 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.

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.

Active Comparator: 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.

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.

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01268995

Locations

Austria
Medical University of Vienna/General Hospital
Vienna, Austria, A-1090

Sponsors and Collaborators

Medical University of Vienna

More Information

No publications provided

Responsible Party:	Dr. Marcus Säemann, Medical University of Vienna
ClinicalTrials.gov Identifier:	NCT01268995 History of Changes
Other Study ID Numbers:	EudraCT: 2009-012712-40
Study First Received:	January 3, 2011
Last Updated:	January 3, 2011
Health Authority:	Austria: Austrian Medicines and Medical Devices Agency

Keywords provided by Medical University of Vienna:

NODAT
kidney transplantation
beta cell function

insulin
Tacrolimus
Cyclosporine A

Additional relevant MeSH terms:

Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Cyclosporins
Cyclosporine
Immunosuppressive Agents
Tacrolimus
Insulin
Insulin, NPH
Enzyme Inhibitors

Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents
Hypoglycemic Agents

ClinicalTrials.gov processed this record on May 19, 2013

Improving Secretion of Insulin in New Onset Diabetes After Renal Transplantation (ISINODAT)