Pancreas Allotransplantation for Diabetic Nephropathy and Mild Chronic REnal fAilure Stage Study

Inclusion Criteria:

Patients will be enroled in this study if they meet all of the following criteria:

- Type 1 diabetic patient aged between 25 and 55 years at the time of randomisation.

- Fasting plasma C-peptide below 0.5 ng/ml.

- Badly controlled diabetes despite an optimized insulin regimen consisting in
continuous subcutaneous insulin infusion (via an insulin pump) or in multiple daily
injections of insulin

- Persistent 24-hour proteinuria above 300 mg/day (a mean from 3 samples) despite
adapted anti-proteinuric therapy for at least 6 months.

- Cystatin C and/or Cr51-EDTA and/or DMSA-Tc scintigraphy measured glomerular
filtration rate from 60 to 90 ml/min.

- No contraindication to pancreas transplant surgery

- Woman of childbearing potential must have a negative serum pregnancy test at
enrolment and must agree to maintain effective birth control during first year of the
study.

- Capable of understanding the purpose and risks of the study, fully informed and given
written informed consent (signed Informed Consent has been obtained).

- Affiliated to national insurance.

Exclusion Criteria:

Patients will be excluded from participating if any of the following criteria apply:

- Patient with any type 2 diabetes and/or fasting plasma C-peptide above 0.5 ng/ml.

- Pregnant woman or breast-feeding mothers.

- Woman of childbearing potential unwilling to maintain effective birth control during
first year of the study

- Second transplant recipient or recipient with a functional grafted organ.

- Proteinuria below 300 mg/day (a mean from 3 samples).

- Albuminemia less than 30 g/l.

- Cystatin C and/or Cr51-EDTA and/or DMSA-Tc scintigraphy measured glomerular
filtration rate lower than 60 ml/min or higher than 90 ml/min.

- Presence of any documented non-diabetic systemic disease potentially affecting the
kidney.

- Known allergy, hypersensibility or intolerance to any known insulin, to any of the
recommended immunosuppressive agents of the study (Thymoglobulin, anti-lymphocyte
serum Fresenius, tacrolimus, cyclosporin, mycophenolate mofetil, mycophenolic acid,
corticosteroids etc), mocrolides antibiotics, or to any compound or excipient of all
these products.

- Currently participating in another clinical trial and/or has taken an investigational
drug within four weeks prior enrolment.

- Diagnosis of new-onset malignancy during 5 years before enrolment.

- Significant, uncontrolled concomitant infections and/or severe diarrhea, vomiting,
active upper gastrointestinal tract malabsorption or active peptic ulcer.

- Patient affected by active B hepatitis (HBsAg positive, HBeAg positive or HBV-DNA
positive) or by active C hepatitis (HCVAb positive; HCV-RNA positive).

- Patient HIV positive.

- Any form of substance abuse, psychiatric disorder or condition which, in the opinion
of the investigator, may complicate communication with the investigator.

- Obesity (body mass index above than 30 kg/m2).

- Severe iliac vessel calcifications impeding surgery.

- Advanced coronary artery disease

- Left ventricular function less than 30%.

- Plasma blood leukocytes less than 2,000 /mm3 or higher than 15,000/mm3

- Plasma blood platelets less 60,000 /mm3 or higher than 500,000/mm3

- Psychological disorders influencing drug compliance.

- Unable, unwilling or unlikely to comply fully with the protocol or the visits
scheduled.