Islet Cell Transplant for Type 1 Diabetes
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 <3,000/ul

 12. Increased risk of bleeding, other chronic hemostasis disorders, or treatment with
 chronic anticoagulant therapy

 13. Recent unresolved acute infection (except for mild skin infection or nail fungal
 infection), or chronic infection

 14. Epstein-Barr Virus (EBV) IgG negative

 15. Any history of malignancy, except for completely resected squamous or basal cell
 carcinoma of the skin or in situ cancer of the cervix

 16. Recent history of non-adherence to medical treatment, or inability to demonstrate
 capacity to comply with strict blood glycemic control and insulin therapy

 17. Psychiatric illness that is untreated, or likely to interfere significantly with study
 compliance despite treatment

 18. Previous organ/tissue transplant, except as noted above

 19. Administration of live attenuated vaccines within 2 months of enrollment

 20. Presence of a chronic disease that must be chronically treated with a contraindicated
 agent

 21. Use of investigational agents within four weeks of enrollment

 22. Active alcohol or substance abuse, including cigarette smoking

 23. Pregnant women, women intending future pregnancy, women of reproductive potential who
 are unable or unwilling to follow effective contraceptive measures prior to study
 entry and for as long as they are on immunosuppression medication, and women presently
 breast feeding are excluded

 24. Individuals without health insurance

 25. History of gastric bypass

 26. Any medical condition that in the opinion of the investigator will interfere with safe
 participation in the trial