Islet Cell Transplant for Type 1 Diabetes

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