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

NCT ID: NCT01067950

Last Updated: 2010-06-02

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-03-31

Brief 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.

Conditions

Type 1 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Isolated Pancreas Transplant

Group Type: EXPERIMENTAL

Isolated Pancreas Transplant

Intervention Type: PROCEDURE

Intensive Insulin Therapy

Group Type: ACTIVE_COMPARATOR

Intensive Insulin Therapy

Intervention Type: DRUG

Interventions

Isolated Pancreas Transplant

Intervention Type: PROCEDURE

Intensive Insulin Therapy

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nantes University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Nantes University Hospital

Principal Investigators

Diego CANTAROVICH, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Nantes University Hospital

Locations

University of Minnesota

Minneapolis, Minnesota, United States

Site Status: NOT_YET_RECRUITING

Albert Einstein Jewish Hospital

São Paulo, , Brazil

Site Status: NOT_YET_RECRUITING

Diabetes Center - Institute for Clinical and Experimental Medicine

Prague, , Czechia

Site Status: NOT_YET_RECRUITING

Hôpital Edouard-Herriot - Hospices Civils de Lyon

Lyon, , France

Site Status: RECRUITING

Centre Hospitalier et Universitaire de Nantes

Nantes, , France

Site Status: RECRUITING

Istituto Scientifico Ospedale San Raffaele

Milan, , Italy

Site Status: NOT_YET_RECRUITING

Azienda Ospedaliero-Universitaria Pisana

Pisa, , Italy

Site Status: NOT_YET_RECRUITING

Countries

United States; Brazil; Czechia; France; Italy

Central Contacts

Diego CANTAROVICH, MD, PhD

Role: CONTACT

diego.cantarovich@chu-nantes.fr

+33(0)240087440

Facility Contacts

David ER SUTHERLAND

Role: primary

Marcelo PEROSA

Role: primary

Frantisek SAUDEK

Role: primary

Charles THIVOLET

Role: primary

Diego CANTAROVICH, MD, PhD

Role: primary

Antonio SECCHI

Role: primary

Ugo BOGGI

Role: primary

Other Identifiers

BRD 09/5-J

Identifier Type: -

Identifier Source: org_study_id