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

NCT01067950 | Unknown Phase 3 DMC

• 1 other identifier: BRD 09/5-J
• Study Type: interventional
• Target: 180
• Locations: 5 countries
• Sites: 7

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

Keywords

isolated pancreas transplant; intensive insulin therapy

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• Secondary objectives are to evaluate and to compare the safety and the efficacy of the two treatments (IPT versus IIT).

  5 years

Study Arms (2)

Isolated Pancreas Transplant

EXPERIMENTAL

Procedure: Isolated Pancreas Transplant

Intensive Insulin Therapy

ACTIVE COMPARATOR

Drug: Intensive Insulin Therapy

Interventions

Isolated Pancreas Transplant PROCEDURE

Isolated Pancreas Transplant

Intensive Insulin Therapy DRUG

Intensive Insulin Therapy

Eligibility Criteria

• Age: 25 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Nantes University Hospital: lead

Study Sites (7)

University of Minnesota

Minneapolis, Minnesota, 55455, United States

NOT YET RECRUITING

Albert Einstein Jewish Hospital

São Paulo, Brazil

NOT YET RECRUITING

Diabetes Center - Institute for Clinical and Experimental Medicine

Prague, Czechia

NOT YET RECRUITING

Hôpital Edouard-Herriot - Hospices Civils de Lyon

Lyon, France

RECRUITING

Centre Hospitalier et Universitaire de Nantes

Nantes, France

RECRUITING

Istituto Scientifico Ospedale San Raffaele

Milan, Italy

NOT YET RECRUITING

Azienda Ospedaliero-Universitaria Pisana

Pisa, Italy

NOT YET RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Diego CANTAROVICH, MD, PhD

  Nantes University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Diego CANTAROVICH, MD, PhD

CONTACT

+33(0)240087440; diego.cantarovich@chu-nantes.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 11, 2010
• First Posted: February 12, 2010
• Study Start: March 1, 2010
• Last Updated: June 2, 2010

Record last verified: 2010-03

Locations

BR (1); FR (2); CZ (1); US (1); IT (2)