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

Type 1 Diabetes Clinical Trial

— PANCREAS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01067950
• Other study ID #: BRD 09/5-J
• Status: Recruiting
• Phase: Phase 3
• First received: February 11, 2010
• Last updated: June 1, 2010
• Start date: March 2010

Study information

• Verified date: March 2010
• Source: Nantes University Hospital
• Contact: Diego CANTAROVICH, MD, PhD
• Phone: +33(0)240087440
• Email: diego.cantarovich[@]chu-nantes.fr
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 25 Years to 55 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetic Nephropathies
• Type 1 Diabetes

Intervention

Procedure:
• Isolated Pancreas Transplant

Drug:
• Intensive Insulin Therapy

Locations

Country	Name	City	State
Brazil	Albert Einstein Jewish Hospital	Sao Paulo
Czech Republic	Diabetes Center - Institute for Clinical and Experimental Medicine	Praha
France	Hôpital Edouard-Herriot - Hospices Civils de Lyon	Lyon
France	Centre Hospitalier et Universitaire de Nantes	Nantes
Italy	Istituto Scientifico Ospedale San Raffaele	Milano
Italy	Azienda Ospedaliero-Universitaria Pisana	Pisa
United States	University of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Nantes University Hospital

Countries where clinical trial is conducted

United States,  Brazil,  Czech Republic,  France,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary end-point is the 5-year evaluation of efficacy/failure rate, a composite end-point including: (i) patient mortality and (ii) renal function impairment		5 years	No
Secondary	Secondary objectives are to evaluate and to compare the safety and the efficacy of the two treatments (IPT versus IIT).		5 years	Yes