A Study Looking at Diabetes in Kidney Transplant Recipients Receiving Immunosuppressive Regimen With or Without Steroids

Study Overview
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Brief Summary
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The purpose of this study is to focus on potential differences in the occurrence of new-onset Diabetes Mellitus (a glucose metabolism disorder) when two different regimens of immunosuppressive treatment are compared.

Detailed Description
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The primary objective of this study is to compare an Immunosuppressive regimen with 10 days of corticosteroids with a regimen with only an optional intra-op bolus of corticosteroids with regard to incidence of new onset Diabetes Mellitus as per the American Diabetic Association (ADA) criteria at any point up to 24 weeks after kidney transplantation.

Official Title
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Investigating New Onset Diabetes Mellitus in Kidney Transplant Recipients Receiving an Advagraf-Based Immunosuppressive Regimen With or Without Corticosteroids - A Multicenter, Two Arm, Randomized, Open Label Clinical Study

Conditions
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Kidney Transplantation

Intervention / Treatment
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* Drug: Advagraf
* Drug: Mycophenolate Mofetil
* Drug: Simulect
* Drug: Corticosteroids


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: End stage kidney disease and a suitable candidate for primary kidney transplantation or re-transplantation (unless the graft was lost from rejection within one year) Receiving a kidney transplant from a deceased or living (non Human Leukocyte Antigen identical) donor with compatible AB0 blood type Female subjects of childbearing potential must have a negative serum or urine pregnancy test at enrollment and must agree to maintain highly effective birth control during the study. A highly effective method of birth control is defined as those which result in a low failure rate (CPMP/ICH/286/95 modified) of less than 1% per year when used consistently and correctly such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomized partner Exclusion Criteria: Receiving or having previously received an organ transplant other than a kidney Cold ischemia time of the donor kidney > 30 hours Panel Reactive Antibody >20% (Highest level in 6 months prior to transplant) Previous renal transplant lost within one year for immunological reasons Receiving a graft from a non-heart-beating donor other than of Maastricht category 3 (withdrawal of support awaiting cardiac arrest) Significant liver disease, defined as having continuously elevated SGPT/ALT and/or SGOT/AST and/or total bilirubin levels ≥ 2 times the upper value of the normal range of the investigational site or is receiving a graft from a hepatitis C or B positive donor Diagnosis of Diabetes Mellitus prior to transplantation (treated with prescribed medications or diet controlled) or where there is evidence of a previous positive Oral Glucose Tolerance Test (OGTT) in the patients medical history or previous diagnosis of gestational diabetes or pre-baseline HbA1C ≥6.5% Requiring initial sequential or parallel therapy with immunosuppressive antibody preparation(s). Requiring ongoing dosing with a systemic immunosuppressive drug prior to transplantation (e.g. for Lupus Disease, FSGN etc) other than minimal levels of immunosuppressant following failure of a previous transplantation without nephrectomy Where Physician considers long term steroid treatment is necessary for the prevention of recurrent auto immune mediated renal disease or if the subject requires ongoing dosing with corticosteroids during the study for any other condition Significant, uncontrolled concomitant infections and/or severe diarrhea, vomiting, active upper gastro-intestinal tract malabsorption or active peptic ulcer Pregnant woman or breast-feeding mother Subject or donor known to be HIV positive Known allergy or intolerance to tacrolimus, macrolide antibiotics, corticosteroids, basiliximab, mycophenolate mofetil or any of the product excipients Evidence of malignant disease within the last 5 years other than Basal Cell Carcinoma or Squamous Cell Carcinoma Currently participating in another clinical trial and/or has taken an investigational drug within 28 days prior to randomization Any form of substance abuse, psychiatric disorder or condition which, in the opinion of the investigator, may complicate communication with the investigator Unlikely to comply with the visits scheduled in the protocol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 10 Days of Steroids<br>Advagraf + Basiliximab + MMF + Steroids (10 days) | Drug: Advagraf<br>* oral<br>* Other names: modified release tacrolimus;Drug: Mycophenolate Mofetil<br>* oral<br>* Other names: CellCept;Drug: Simulect<br>* IV<br>* Other names: Basiliximab;Drug: Corticosteroids<br>* IV & oral<br>* Other names: methylprednisolone;|
| Experimental: Optional Steroid bolus only<br>Advagraf + Basiliximab + MMF + Steroids (bolus only) | Drug: Advagraf<br>* oral<br>* Other names: modified release tacrolimus;Drug: Mycophenolate Mofetil<br>* oral<br>* Other names: CellCept;Drug: Simulect<br>* IV<br>* Other names: Basiliximab;Drug: Corticosteroids<br>* IV & oral<br>* Other names: methylprednisolone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnosis of new onset Diabetes Mellitus as per ADA criteria at any point up to 24 weeks after kidney transplantation |  | up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy failure using a composite endpoint consisting of graft loss, biopsy confirmed acute rejection or graft dysfunction |  | up to 6 months | 
| Positive Oral Glucose Tolerance Test |  | 8 weeks | 
| Repeat Positive Oral Glucose Tolerance Test |  | 6 months | 
| Renal function |  | at 6 months | 
| Acute Rejections |  | up to 6 months | 
| Biopsy confirmed acute rejections |  | up to 6 months | 
| Subject survival |  | up to 6 months | 
| Graft survival |  | up to 6 months | 
| Change from Baseline in HbA1C levels |  | Baseline, week 12 and week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney, Diabetes Mellitus, Transplant, Immunosuppression