Islet Cell Transplantation in Patients With Type I Diabetes With Previous Kidney Transplantation

Study Overview
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Brief Summary
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This single center phase 2 clinical trial, is designed for confirming the efficacy and safety of sequential islet allotransplantation with steroid free immunosuppression in patients with previous kidney transplantation.

Detailed Description
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The beneficial effects of glycemic control on both survival and function of transplanted kidneys in patients with type 1 diabetes mellitus have been recognized. The purpose of this study is to reverse hyperglycemia and insulin dependency, by islet cell transplantation, in patients with type 1 diabetes mellitus who have a stable kidney allograft. The study primary efficacy endpoint is graft survival defined as insulin independence and HbA1c < 8% at 1 year post first transplant. Secondary outcomes are graft function and metabolic control The immunosuppression protocol for the kidney graft was converted to sirolimus+tacrolimus regimen 6 months before islet transplantation to exclude negative effects on kidney graft function.

Official Title
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Phase 2 Study of Islet Cell Transplantation in Patients With Type I Diabetes With Previous Kidney Transplantation With Steroid Free Immunosuppression

Conditions
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Type 1 Diabetes, Organ Transplantation, Immunosuppression

Intervention / Treatment
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* Procedure: islet transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 1 diabetes mellitus. Documentation of negative basal and stimulated C-peptide and diagnosis of diabetes for at least 5 years. Recipient of renal transplant with good function (creatinine clearance >/=60 ml/min) Stable immunosuppression consisting of any combination of sirolimus, tacrolimus for at least 6 months, without major complications Ability to give informed consent. Age greater than or equal to 18 years or less than or equal to 65 years No evidence of liver disease (liver enzymes < twice the upper limit of normal) Exclusion Criteria: Age below 18 years and above 65 years Significant cardiovascular disease, including non-correctable coronary artery disease and/or recent myocardial infarction(within last 12 months); extensive peripheral vascular disease not correctable by surgery, unstable angina Untreated proliferative retinopathy. Recent Cerebrovascular accident (within last 12 months) Recent unresolved acute infection, or chronic infection, including tuberculosis, HIV, HBV, HCV, CMV or positive skin test for TB Any history of malignancy, except squamous or basal skin cancer or in situ cancer of the cervix. History of non-compliance, or inability to demonstrate capacity to comply with strict blood glycemic control and insulin pump therapy. Psychiatric illness that is untreated, or likely to interfere significantly with transplantation despite treatment. Pregnant women, women intending future pregnancy, women of reproductive potential who are unable or unwilling to follow effective contraceptive measures for the duration of immunosuppressive therapy Fasting C-peptide > 0.2 ng/ml Creatinine > 25mg/l Alkaline phosphatase, total bilirubin, Alanine Aminotransferase (ALT)or Aspartate Aminotransferase (AST) > twice the upper limit of normal Significant liver disease (elevation of liver enzymes > twice the upper limit of normal for each of ALT and AST, liver masses including portal vein thrombosis, evidence of portal hypertension, or significant, untreated gallbladder disease (i.e., gallstones).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Islet transplantation
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: islet transplantation<br>Islet transplantation | Procedure: islet transplantation<br>* Islet transplantation consisted of up to three sequential fresh islet infusions within three months. Access to the portal vein was gained under general anesthesia by percutaneous catheterisation of a peripheral portal branch under ultrasound guidance or by surgical catheterisation of a small mesenteric vein.<br>* Other names: percutaneous catheterisation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite criteria: insulin independence and Glycosylated Hemoglobin (HbA1c) under 8% at one year after the transplantation | Percent of insulin-independent patients with a Glycosylated Hemoglobin (HbA1c) under 8% at one year after injection of approximately 10,000 islets equivalents / kg (IE/kg). | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of adverse events | The number of adverse events related to the procedure and to the immunosuppression | 1 year | 
| Number of severe episodes of hypoglycemia | Number of severe episodes of hypoglycemia (requiring the use of third) | 1 year | 
| Evaluation of Diabetes complications | Evaluation of Diabetes complications: retinopathy, neuropathy, nephropathy | 1 year | 
| Lipid metabolism | Lipid metabolism assessed by measurement of total cholesterol and HDL cholesterol, triglycerides, ApoA1, apoB, apoE, free fatty acids and lipid. | 1 year | 
| Evaluation of kidney function | Evaluation of kidney function (creatinine, creatinine clearance,proteinurie) | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes type 1, kidney transplantation, islet, hypoglycemia