Solitary Islet Transplantation for Type 1 Diabetes Mellitus Using Steroid Sparing Immunosuppression

Study Summary

This study will test whether a new islet transplant procedure will enable patients with type 1 diabetes mellitus to stop insulin therapy. Islets are cell clusters in the pancreas that contain insulin-producing cells. The new procedure features three important advances, first developed by a group in Edmonton, Canada, over the way islet transplants have traditionally been performed: 1) the islets are transplanted immediately after they are removed from the donor; 2) islets are transplanted from two different donors in order to obtain the number of islets in a normal pancreas; and 3) the anti-rejection drug regimen is designed to reduce the harmful side effects of "conditioning" chemotherapy. (In the standard transplant procedure, patients receive intensive chemotherapy following the transplant. This study will use no radiation and lower-dose chemotherapy.) Patients between the ages of 18 and 65 with the diagnosis of type 1 diabetes mellitus for at least 5 years may be eligible for this study. Candidates will be screened with a medical history and physical examination, blood tests, chest X-ray and tuberculin skin test, electrocardiogram and exercise test for heart function, abdominal ultrasound, psychological evaluation, and an arginine stimulated c-peptide test. The latter test determines if the patient is producing any insulin. Eligibility is restricted to patients who make no insulin at all. The study has an active phase lasting 15 months and follow-up that continues indefinitely. Patients will receive 10,000 "islet equivalents" per kilogram (2.2 pounds) of body weight. This will likely require two separate transplant procedures from two donors. Before the first surgery, patients will be given anti-rejection (immune suppressing) drugs, including FK506 and rapamycin (orally) and daclizumab (intravenously). The islets will be infused through a tube placed in the portal vein (the large vein that feeds the liver). After surgery, patients will receive insulin intraveno

Primary Outcome

To reproduce and improve upon a pilot series of clinical islet transplants from Edmonton, using steroid free immunosuppression in conjunction with defined isolation, characterization and transplantation protocols. The study will determine the number of patients receiving an islet allotransplant who are insulin independent at 1 year post-transplant of at least 10,000 IEQ/kg body weight.

Interventions

• DRUG Islet Transplantation