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

This is an interventional treatment trial for Type 1 Diabetes focused on measuring isolated pancreas transplant, intensive insulin therapy Read More

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.