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

Conditions:Renal Impairment / Chronic Kidney Disease, Diabetes
Therapuetic Areas:Endocrinology, Nephrology / Urology
Age Range:25 - 55
Start Date:March 2010
Contact:Diego CANTAROVICH, MD, PhD

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International, Multicenter, Prospective, Randomized, Parallel Group, Open Label Protocol to Evaluate Safety and Efficacy of Isolated Pancreas Transplantation Compared to Intensive Insulin Therapy in Type 1 Diabetic Patients With Overt Diabetic Nephropathy and Mildly Reduced Renal Function

Current medical therapies are not able to prevent progression of established
macroproteinuira (i.e. diabetic nephropathy) to end-stage renal failure in type 1 (insulin
dependent) diabetic patients. In this setting, proteinuria is a major risk factor for
mortality. Pancreas transplantation, on the contrary, can revert diabetic nephropathy and
thereby prevent end-stage chronic renal failure, with theoretically lower risk of death as
compared to current medical therapies.The main objective of this study is to assess
superiority of isolated pancreas transplantation versus intensive exogenous insulin therapy
in type 1 diabetic patients with overt diabetic nephropathy and mildly reduced renal
function. The primary endpoint is a composite efficacy/failure end-point including: patient
mortality and renal function impairment during 5 years in patients with badly controlled
diabetes and nephropathy resisting to up-to-date nephroprotective therapies.Main secondary
objectives are safety and efficacy of both regimens, including proteinuria and renal
histology evaluation, metabolic control and quality of life, acute and chronic extrarenal
complications of diabetes, pancreas survival and all risks related to the transplant
procedure (anaesthesia, surgery and immunosuppression side-effects) and to the intensive
insulin therapy management.

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

- 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

- 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
We found this trial at
Minneapolis, Minnesota 55455
(612) 625-5000
Univ of Minnesota With a flagship campus in the heart of the Twin Cities, and...
Minneapolis, MN
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