Title
Study of Islet Transplantation in Type 1 Diabetic Kidney Transplant Recipients
Islet Transplantation in Type 1 Diabetic Kidney Allograft Recipients
Phase
Phase 1/Phase 2Lead Sponsor
Harvard UniversityStudy Type
InterventionalStatus
Completed Results PostedIndication/Condition
Diabetes Mellitus, Type IIntervention/Treatment
allogeneic pancreatic islet cells etanercept ...Study Participants
7The 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
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.
Islet after kidney transplant in patients with type I diabetes.
Given as induction for islet cell transplant
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.
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.
| Event Type | Organ System | Event Term | Islet Transplant |
|---|
Subjects will have a decrease in HbA1c of at least >1%
Proteinuria and serum creatinine will be stable or decreased as compared to pre-transplant values
Improvement of frequency of interventions and from changes in reported visual acuity with optical refraction and severity of diabetic retinopathy
Loss of allograft survivial (return to dialysis, retransplant, death) and Renal allograft function meausred by SCr
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).
Subjects will have a decrease in severe hypoglycemic events
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.
