Islet Cell Transplant for Type 1 Diabetes (TCD)

City of Hope

Status and phase: Active, not recruiting; Phase 2

Conditions: Type 1 Diabetes Mellitus

Treatments: Biological: Allogenic Human Islet Cells; Drug: Immunosuppressive Agents; Drug: Gastrin 17

Study type: Interventional

Funder types: Other

Identifiers

NCT01909245

12446

Details and patient eligibility

About

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.

Enrollment: 10 patients

Sex: All

Ages: 18 to 68 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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10 participants in 1 patient group

Single Arm Study

Experimental group

Description:

Allogenic Human Islet Cell Transplant with immunosuppression

Treatment:

Drug: Gastrin 17

Drug: Immunosuppressive Agents

Biological: Allogenic Human Islet Cells