Delayed Mycophenolate Mofetil in Single-Donor Islet Allotransplantation in Type 1 Diabetes

University of Minnesota (UMN)

Status and phase: Completed; Phase 2; Phase 1

Conditions: Hypoglycemia; Type 1 Diabetes

Treatments: Biological: Allogeneic islets of Langerhans transplant

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00285233

0006M55241

Details and patient eligibility

About

The objective of this study is to assess the safety and efficacy of islet allotransplantation for the reestablishment of stable glycemic control in patients with type 1 diabetes, using anti-thymocyte globulin induction immunosuppression with sirolimus, mycophenolate mofetil and low dose tacrolimus maintenance immunosuppression.

Full description

To assess the safety and efficacy of a new single-donor islet allotransplant protocol focusing on minimization of ischemic damage by the two-layer pancreas preservation technique, attenuation of posttransplant nonspecific inflammatory responses by etanercept and anti-thymocyte globulin, deletion/inactivation of autoreactive T cells by anti-thymocyte globulin and daclizumab induction immunotherapy, and potent yet non-diabetogenic maintenance immunosuppression with sirolimus and delayed mycophenolate mofetil instead of tacrolimus for the reestablishment of stable glycemic control in recipients with type 1 diabetes.

Enrollment: 8 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Primary islet allotransplant

2. Type 1 diabetes mellitus, complicated by at least one of the following situations that persist despite intensive efforts in close cooperation with their diabetes care team:

   1. Metabolic lability/instability;
   2. Reduced awareness of hypoglycemia;
   3. Persistently poor glucose control (as defined by HgbA1c>10% at the end of six months of intensive management efforts with the diabetes care team);
   4. Progressive secondary complications.

3. Age 18 and older

4. Able to give written informed consent

Exclusion criteria

1. Known hypersensitivity to rabbit proteins.
2. Presence of history of panel-reactive anti-HLA antibodies (>10%).
3. Insufficient cardiovascular reserve.
4. Creatinine clearance <60 mL/min/m2.
5. Portal hypertension, abnormal liver enzyme tests, or history of significant liver disease.
6. History of malignancy within 5 years.
7. Active peptic ulcer disease.
8. Severe unremitting diarrhea or other gastrointestinal disorders potentially interfering with the ability to absorb oral medications.
9. Pregnancy or breast-feeding.
10. Active infections.
11. Serological evidence of infection with HIV, or HBsAg or HCVAb positive within the previous 12 months prior to transplantation.
12. Negative screen for Epstein-Barr Virus (EBV) by an EBNA method
13. Evidence of infiltrate, cavitation, or consolidation on chest x-ray during pre-study screening.
14. Schizophrenia, bipolar disorder, or major depression that is unstable or uncontrolled on current medications.
15. Ongoing substance abuse; drug or alcohol.
16. Recent history of noncompliance.
17. Any medical condition that, in the opinion of the investigator, will interfere with the safe completion of the trial.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

---

8 participants in 1 patient group

1

Experimental group

Treatment:

Biological: Allogeneic islets of Langerhans transplant