The International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes--chapter 4: Pre-clinical efficacy and complication data required to justify a clinical trial.

Pre-clinical efficacy and complication data required to justify a porcine islet transplantation clinical trial have been considered. To be relevant to clinical islet transplantation, pre-clinical data should be obtained in a pig-to-diabetic non-human primate (NHP) model. In view of the difficulties of maintaining immunosuppressed NHPs for long periods of time, flexibility must be allowed with regard to the following recommendations. A pre-clinical trial would be deemed a success if five of eight consecutive experiments in NHPs with proven diabetes meet the following guidelines. 1. The fasting and non-fasting blood glucose levels have been maintained in the NHP at approximately <150 mg/dl (>8.3 mmol/l) and <200 mg/dl (11.1 mmol/l), respectively, throughout a 6-month follow-up period (preferably with observations in one or two NHPs extending to 12 months). 2. After the transplantation of adult or fetal/neonatal pig islets, no or greatly reduced exogenous insulin has been required after the development of a state of normoglycemia (that may take approximately the first 4 weeks for adult and 12 weeks for fetal/neonatal islets, respectively), except under exceptional, temporary circumstances. 3. Sequential intravenous glucose tolerance tests [at 1, 3, 6 (and 12) months post-transplantation] or arginine stimulation tests have indicated a significant response to glucose in the form of porcine C-peptide in the absence of a significant response of NHP C-peptide. 4. Histologic study of the native pancreas (if present) after necropsy indicates no or minimal insulin-positive beta cells, and histologic examination of the liver or other site of islet transplantation indicates multiple viable insulin-positive cells. 5. Numerous or serious life-threatening complications have not been associated with the transplantation procedure, immunosuppressive regimen, tolerance-inducing regimen, or encapsulation of the islets. Pre-clinical trials in which the recipient NHPs do not require continuing immunosuppressive therapy (e.g., when encapsulated islets have been transplanted) may possibly be considered acceptable as a basis for a clinical trial with slightly less stringent requirements with regard to points (1) and (2), but would be expected to provide evidence that points (3), (4), and (5) had been achieved.