First update of the International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes--Chapter 6: patient selection for pilot clinical trials of islet xenotransplantation.

ABSTRACT

Patients in whom type 1 diabetes is complicated by impaired awareness of hypoglycemia and recurrent episodes of severe hypoglycemia are candidates for islet or pancreas transplantation if severe hypoglycemia persists after completion of a structured stepped care approach or a formalized medical optimization run-in period that provides access to hypoglycemia-specific education including behavioral therapies, insulin analogs, and diabetes technologies under the close supervision of a specialist hypoglycemia service. Patients with type 1 diabetes and end-stage renal failure who cannot meet clinically appropriate glycemic goals or continue to experience severe hypoglycemia after completion of a formalized medical optimization program under the guidance of an expert diabetes care team are candidates for islet or pancreas transplantation either simultaneously with or after a previous kidney transplant. Similarly, patients with type 2 diabetes and problematic hypoglycemia or renal failure who meet these criteria are considered candidates for islet replacement. Likewise, patients with pancreatectomy-induced diabetes in whom an islet autograft was not available or deemed inappropriate are candidates for islet or pancreas transplantation if extreme glycemic lability persists despite best medical therapy. To justify participation of these transplant candidates in early-phase trials of porcine islet cell products, lack of timely access to islet or pancreas allotransplantation due to allosensitization, high islet dose requirements, or other factors, or alternatively, a more favorable benefit-risk determination associated with the xenoislet than the alloislet or allopancreas transplant must be demonstrated. Additionally, in non-uremic xenoislet recipients, the risks associated with diabetes must be perceived to be more serious than the risks associated with the xenoislet product and the rejection prophylaxis, and in xenoislet recipients with renal failure, the xenoislet product and immunosuppression must not impact negatively on renal transplant outcomes. The most appropriate patient group for islet xenotransplantation trials will be defined by the specific characteristics of each investigational xenoislet product and related technologies applied for preventing rejection. Selecting recipients who are more likely to experience prolonged benefits associated with the islet xenograft will help these patients comply with lifelong monitoring and other public health measures.