1. To determine and compare the efficacy of Tacrolimus/Rapa versus Tacrolimus/MMF-based immunosuppression (in conjunction with initial short-term steroids and polyclonal antibody administration) in Type 1-diabetic patients undergoing simultaneous pancreas/kidney allograft transplantation.
2. To evaluate the safety of Tacrolimus/Rapa versus Tacrolimus/MMF in terms of drug-related complications and overimmunosuppression-associated complications, particularly under monitoring of the pharmacokinetic profile of all drugs administered.

Condition	Intervention	Phase
Diabetes Mellitus, Type 1 Diabetic Nephropathy	Drug: sirolimus versus mycophenolate mofetil	Phase III

Further Study Details: 

Primary Outcomes: At 1 year:Incidence of biopsy-proven (kidney) rejection episodes.
Secondary Outcomes: SECONDARY ENDPOINTS: At 6 months and 1 year; * Kidney/Pancreas function (at 6 months and 1 year):; - Kidney function will be measured by:; - S- creatinine; - Creatinine clearance; - Pancreas function will be measured by:; - Fasting Glucose level (< 123 mg/dl); - HbA1C; - Need for insulin therapy; - Need for oral drugs; * At 6 months and 1 year:; - Patient and graft survival; - Lipid profile; - Infections; - Side effects; - Blood Pressure; - Treatment failure for any reason, such as permanent discontinuation of a drug, graft loss or death.; * % of steroid free patients: at 6 months and 1 year.
Expected Total Enrollment:  228

This will be a controlled, randomised study, to be performed in 15-20 pancreas transplantation centers throughout Europe. Patients will be randomised into one of two treatment groups. Group 1 will receive Tacrolimus and Mycophenolate Mofetil (= best group in EuroSPK001 trial). Group 2 will receive Tacrolimus and Sirolimus. Both groups will receive in association short-term corticosteroids and polyclonal antibody preparation. Patients will be randomly assigned to one of the 2 treatment groups in a 1:1 ratio before transplantation. The study will last 3 years, with a first interim analysis of the data at 6 months and a complete analysis at 1 year.

Ages Eligible for Study:  18 Years   -   55 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

1. Male or female patients, of 18 to 55 years of age, with end-stage, C-peptide-negative, Type 1-diabetic nephropathy.
2. Female patients of childbearing age must have a negative pregnancy test and must agree to maintain effective birth control practice throughout the study period (3 years).
3. Patient must have signed the Patient Informed Consent Form.
4. Patient must receive a primary simultaneous pancreas/kidney (SPK) cadaveric transplant, with either intestinal or bladder and either portal or systemic venous drainages.

Exclusion Criteria:

1. Patient is pregnant or breastfeeding.
2. Patient is allergic or intolerant to Mycophenolate Mofetil, Sirolimus, Tacrolimus or other macrolides, or any compounds structurally related to these compounds.
3. Patient has a positive T-cell crossmatch on the most recent serum specimen.
4. Patient is known for active liver disease or has significant liver disease, defined by ASAT and ALAT serum levels greater than 3 times the upper limit of normal.
5. Patient has malignancy or history of malignancy, with the exception of adequately treated localised squamous cell or basal cell carcinoma, without recurrence.
6. Patient has been included in another clinical trial protocol for any investigational drug within 4 weeks prior to randomisation.
7. Patient has any form of substance abuse, psychiatric disorder or condition, which, in the opinion of the investigator, may invalidate communication.
8. Patient receives a SPK transplant from a living donor, or receives segmental pancreatic transplant, or a previous kidney transplant alone.
9. Pancreatic duct occlusion technique .

10. Donor is older than 55 years of age.

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Austria
      UNIVERSITÄTSKLINIK, Innsbruck,  6020,  Austria
Belgium
      Cliniques Universitaires Saint Luc, Brussels,  1200,  Belgium
      UZ Gasthuisberg, Leuven,  3000,  Belgium
      UZ Gent, Gent,  9000,  Belgium
Czech Republic
      Institute for clinical and experimental medicine-IKEM, Prague,  14021,  Czech Republic
Germany
      Klinikum Grosshadern-University of Munich, Munich,  81366,  Germany
      Klinikum Innenstadt der Universität München, Munich,  90336,  Germany
      Charite Campus Virchow Klinikum, Berlin,  13353,  Germany
      Chirurgische UNIVERSITÄTSKLINIK, Freiburg,  79111,  Germany
      Knappschaftskrankenhaus, Bochum-Langendreer,  44892,  Germany
      Goethe University, Frankfurt am Main,  60590,  Germany
Israel
      Tel Aviv Sourasky Medical Center, Tel Aviv,  64239,  Israel
Spain
      Hospital Clinico, Barcelona,  08036,  Spain
Switzerland
      Hôpital Cantonal de Geneve, Geneva,  1211,  Switzerland

Study chairs or principal investigators

Jean-Paul Squifflet, MD,PhD,  Study Chair,  SPEAKER FOR THE EUROSPK STUDY GROUP   

Study ID Numbers:  EUROSPK002
Last Updated:  August 31, 2005
Record first received:  August 31, 2005
ClinicalTrials.gov Identifier:  NCT00140543
Health Authority: Belgium: Directorate general for the protection of Public health: Medicines
ClinicalTrials.gov processed this record on 2005-09-13