Islet Cell Transplant for Type 1 Diabetes

City of Hope National Medical Center, located in Duarte, CA, is hosting a clinical study on islet cell transplantation, an experimental procedure being evaluated as a treatment for patients with type 1 diabetes. Islet cell transplantation involves taking insulin-producing cells from organ donors and transplanting them into the liver of a patient with diabetes. Once transplanted, the islets produce insulin, which can improve blood sugar control and eliminate the need to inject insulin or use an insulin pump. Anti-thymocyte globulin (ATG) and alemtuzumab (Campath) are anti-rejection medications that work by decreasing a patient's T-cells. T-cells are special white blood cells that recognize and destroy unwanted things like infections but can also attack transplanted cells and organs. Reducing the number of T-cells at the time of transplant may protect islets and improve long-term transplant success. In previous research studies, islet transplantation has been successful in reducing low blood sugar episodes, improving overall blood sugar control, and in some cases, allowing patients with type 1 diabetes to stop taking insulin. The purpose of this study is to determine if islet cell transplantation using ATG or alemtuzumab, along with additional medications to prevent the body from rejecting the transplanted cells, is a safe and effective treatment for type 1 diabetes. Study participants may receive up to three islet transplants and will be followed for five years to monitor blood sugar control, islet transplant function, and changes in quality of life.

Three different categories of patients with Type 1 Diabetes will be considered for study participation: * Naïve islet transplant alone (nITA) candidates: T1D patients complicated by frequent/severe hypoglycemia, hypoglycemia unawareness, AND/OR otherwise unstable blood glucose control who have not received a previous transplant (except for a failed pancreas more than 6 months prior to screening) * Repeat transplant (RT) candidates: T1D patients who have received two or fewer previous islet transplants \> 1 month prior to screening, but continue to require exogenous insulin treatment or have an HbA1c \> 6.5% * Islet after kidney transplant (IAK) candidates: T1D patients with a history of successful renal transplant \> 3 months prior to screening Inclusion criteria for all candidates: 1. Age 18-68 years 2. Type 1 diabetes mellitus for at least 5 years 3. Ability and willingness to comply with post-transplant regimen, including taking anti-rejection medications, use of reliable contraception, frequent clinic visits, lab tests, careful recording of blood glucose values, insulin doses and medications, and completing detailed follow-up studies Additional Inclusion Criteria nITA Candidates Only 4. Unstable blood sugar control characterized by: Frequent hypoglycemia (blood glucose ≤ 54 mg/dl more than once per week) -AND/OR- Hypoglycemia unawareness (Clarke score of 4 or more) -AND/OR- One or more severe hypoglycemic episodes in 12 months preceding enrollment. -AND/OR- Erratic blood glucose levels that interfere with daily activities -AND/OR- One or more hospital visits for diabetic ketoacidosis in the 12 months preceding enrollment Additional Inclusion Criteria for RT Candidates Only 5. One or two or previous islet transplants \> 1 month prior to screening with continuing insulin requirements and/or HbA1c \> 6.5% Additional Inclusion Criteria for IAK Candidates Only 6. Successful kidney transplant \> 3 months prior to screening 7. Stable maintenance immunosuppression consisting of tacrolimus alone or in conjunction with sirolimus, mycophenolate mofetil, myfortic or azathoprine; or cyclosporine in conjunction with sirolimus, mycophenolate mofetil, or myfortic +/- ≤ 10 mg/day corticosteroids 8. No history of acute rejection related to kidney graft in last 12 months and low risk of rejection 9. Under continuing care of physician for kidney graft, who has provided letter in support of candidate's consideration for study participation Exclusion Criteria: 1. Body Mass Index (BMI) \> 33 2. Insulin requirements \> 1.2 units/kg/day 3. Known sensitization to both rATG -and- alemtuzumab 4. Significant kidney dysfunction 5. Significant liver/gall bladder disease 6. Significant cardiovascular disease 7. Active proliferative retinopathy 8. High blood pressure despite appropriate treatment 9. High cholesterol/triglycerides despite appropriate treatment 10. Anemia or other blood disorders that require medical treatment 11. WBC \