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

This study has been terminated.
(It was impossible to recruit the scheduled number of patients)
Sponsor:
Information provided by:
Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT01268995
First received: January 3, 2011
Last updated: NA
Last verified: January 2011
History: No changes posted
  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:


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.

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 July 24, 2014