Study of Islet Transplantation in Type 1 Diabetic Kidney Transplant Recipients

Study Overview
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Brief Summary
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The purpose of the study is to learn if islet transplantation is an effective treatment for Type 1 diabetes in people who have had a kidney transplant. The primary objectives of the study are: - To set up islet transplantation in patients who have had a kidney transplant and who are using an immunosuppressive regimen that works The Secondary objective of the study is: To find out if successful islet transplantation leads to improved metabolic control and reduced renal complication from diabetes

Detailed Description
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Patients will receive (an) infusion(s) of in vitro cultured islets with the goal of achieving insulin independence. For the first islet transplant, patients will receive induction therapy with rabbit anti-thymocyte globulin (ATG, 5 doses) and will remain on their maintenance immunosuppression regimen already in place for their renal allograft. Induction therapy for subsequent transplants will be 2doses of basiliximab. All patients will receive Etanercept to promote engraftment.

Official Title
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Islet Transplantation in Type 1 Diabetic Kidney Allograft Recipients

Conditions
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Diabetes Mellitus, Type I

Intervention / Treatment
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* Biological: Purified Pancreatic Islets
* Drug: Etanercept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects Age 18 to 70 years of age Have insulin dependent Diabetes Mellitus Type 1 Are post-renal transplant on maintenance immunosuppression with stable renal function HbA1c > 7.5% or < 7.5% and hypoglycemia unawareness Exclusion Criteria: Weight more than 90 kg Insulin requirement > 60 Units/day Other (non-kidney) organ transplants except prior failed pancreatic graft. Untreated or unstable proliferative diabetic retinopathy Presence of de novo antibody production since the renal allograft or either Class I or Class II panel-reactive anti-HLA antibodies Active infection Negative screen for Epstein-Barr virus (EBV) Any history of malignancy except for completely resected squamous or basal cell carcinoma of the skin History of Factor V Leiden mutation Any coagulopathy or medical condition requiring long-term anticoagulant therapy (e.g. warfarin) after transplantation (low-dose aspirin treatment is allowed) or subjects with international normalized ratio (INR) > 1.5 Severe co-existing cardiac disease Persistent elevation of liver function tests at the time of study entry Acute or chronic pancreatitis Male subjects with elevation of prostate specific antigen Pregnancy Positive screen for polyoma (BK) virus Untreated hyperlipidemia Recent hemorrhagic stroke Factors associated with an increased risk of bleeding Contact PI for complete Incl-Excl criteria list.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Islet transplant<br>Patients will receive (an) infusion(s) of in vitro cultured islets with the goal of achieving insulin independence. For the first islet transplant, patients will receive induction therapy with rabbit anti-thymocyte globulin (ATG, 5 doses) and will remain on their maintenance immunosuppression regimen already in place for their renal allograft. Induction therapy for subsequent transplants will be 2 doses of basiliximab. All patients will receive Etanercept to promote engraftment. | Biological: Purified Pancreatic Islets<br>* Islet after kidney transplant in patients with type I diabetes.<br>Drug: Etanercept<br>* Given as induction for islet cell transplant<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin Independence With Both an HbA1c ≤ 6.5% and no Severe Hypoglycemic Events at 1 Year After the First Islet Transplant or a Reduction in HbA1c of at Least 1 Point and no Severe Hypoglycemic Events at 1 Year After the First Islet Transplant. |  | 1 year after the subject's first islet transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Decrease in HbA1c | Subjects will have a decrease in HbA1c of at least >1% | 1 year after subject's first islet transplant | 
| Stable or Decrease in Urinary Albumin and Creatinine Ratio and Serum Creatinine | Proteinuria and serum creatinine will be stable or decreased as compared to pre-transplant values | 1 year after subjects initial islet transplant | 
| An Absence Cardiovascular Events, Cerebral Vascular Accident, and Myocardial Infarction |  | 1 year after the subject's first islet transplant | 
| Impact on Vision | Improvement of frequency of interventions and from changes in reported visual acuity with optical refraction and severity of diabetic retinopathy | 1 year after the subject's first islet transplant | 
| Absence of Negative Renal Impact Measures | Loss of allograft survivial (return to dialysis, retransplant, death) and Renal allograft function meausred by SCr | 1 year after the subject's first islet transplant | 
| Improvement of Metabolic Control | Whether there is an improvement in metabolic control in IAK will be evaluated based on improvement in basal c-peptide levels, MMTT, insulin requirements, and c-peptide to glucose, creatinine ratio (CPGCR). | 1 year after the subject's first islet transplant | 
| Number of Participants With a Decrease of Severe Hypoglycemic Events | Subjects will have a decrease in severe hypoglycemic events | 1 year after subject's first transplant | 
| Reduction of Insulin Requriements | Evidence of partial success will be considered for subjects who have a reduction in insulin requirements but who are not insulin independent. This will be assessed by comparing the pre-transplant insulin requirement expressed as insulin units per kg per day with the requirement preceding subsequent islet transplants and the insulin requirements at 6 months and 1, 2, and 3 years after the first and last transplant. | 1 year after the subject's first islet transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type I diabetes, Islet after Kidney Transplant, Islet transplantation