Study of Islet Transplantation in Type 1 Diabetic Kidney Transplant Recipients

Phase 1

Completed

Conditions: Diabetes Mellitus, Type I

Interventions: Biological: Purified Pancreatic Islets
Drug: Etanercept

Registration Number: NCT00888628

Lead Sponsor: Massachusetts General Hospital

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 7

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Islet transplant	Purified Pancreatic Islets	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.
Islet transplant	Etanercept	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Stable or Decrease in Urinary Albumin and Creatinine Ratio and Serum Creatinine	1 year after subjects initial islet transplant	Proteinuria and serum creatinine will be stable or decreased as compared to pre-transplant values
Impact on Vision	1 year after the subject's first islet transplant	Improvement of frequency of interventions and from changes in reported visual acuity with optical refraction and severity of diabetic retinopathy
Improvement of Metabolic Control	1 year after the subject's first islet transplant	Whether there is an improvement in metabolic control in IAK will be evaluated based on improvement in 1. basal c-peptide levels, 2. MMTT, 3. insulin requirements, and 4. c-peptide to glucose, creatinine ratio (CPGCR).
Number of Participants With a Decrease of Severe Hypoglycemic Events	1 year after subject's first transplant	Subjects will have a decrease in severe hypoglycemic events
Reduction of Insulin Requriements	1 year after the subject's first islet transplant	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.
An Absence Cardiovascular Events, Cerebral Vascular Accident, and Myocardial Infarction	1 year after the subject's first islet transplant
Number of Participants With a Decrease in HbA1c	1 year after subject's first islet transplant	Subjects will have a decrease in HbA1c of at least \>1%
Absence of Negative Renal Impact Measures	1 year after the subject's first islet transplant	Loss of allograft survivial (return to dialysis, retransplant, death) and Renal allograft function meausred by SCr