Treatment of Type I Diabetes by Islet Transplantation Into the Gastric Submucosa Study Protocol

Exclusion Criteria

• •1. Weight more than 100 kg or body mass index (BMI) \> 30 kg/m2.
• •2. Insulin requirement of \>1.0 IU/kg/day or \<15 U/day.
• •3. Other (non-kidney) organ transplants except prior failed pancreatic graft where graft failure is attributed to thrombosis within the first 4 weeks or to other technical reasons that require graft pancreatectomy; with the graft pancreatectomy occurring more than 6 months prior to enrollment.
• •4. Untreated or unstable proliferative diabetic retinopathy.
• •5. Blood Pressure: SBP \> 160 mmHg or DBP \>100 mmHg despite treatment with antihypertensive agents.
• •6. Calculated GFR of ≤ 40 mL/min/1.73 m2 using the subject's measured serum creatinine and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. (59)
• •7. Proteinuria (albumin/creatinine ratio or ACr \> 300mg/g) of new onset since kidney transplantation.
• •8. Calculated panel-reactive anti-HLA antibodies \> 50%. Subjects with calculated panel reactive anti-HLA antibodies ≤ 50% will be excluded if any of the following are detected:
• •* Positive cross-match
• •* Islet donor-directed anti-HLA antibodies detected by Luminex® Single Antigen/specificity bead assay including weakly reactive antibodies that would not be detected by a flow cross-match
• •9. For female subjects: Positive pregnancy test, presently breast-feeding, or unwillingness to use effective contraceptive measures for the duration of the study and 4 months after discontinuation. For male subjects: intent to procreate during the duration of the study or within 4 months after discontinuation or unwillingness to use effective measures of contraception. Oral contraceptives, Norplant®, Depo-Provera®, and barrier devices with spermicide are acceptable contraceptive methods; condoms used alone are not acceptable.
• •10. Active infection including hepatitis B, hepatitis C, HIV, or TB. A positive skin test (PPD) in itself is not an exclusion, and will be followed up by a QuantiFERON® gold assay.
• •11. Negative screen for EBV IgG.
• •12. Invasive Aspergillus, Histoplasmosis, and Coccidioidomycosis infection within 1 year prior to study entry.
• •13. Any history of malignancy except for completely resected squamous or basal cell carcinoma of the skin.
• •14. Known active alcohol or substance abuse.
• •15. Severe co-existing cardiac disease, characterized by any one of these conditions:
• •* Recent MI (within past 6 months),
• •* Evidence of ischemia on functional cardiac exam within the last year,
• •* Left ventricular ejection fraction \< 30%,
• •* Valvular disease requiring replacement with prosthetic valve.
• •16. Persistent elevation of liver function tests at time of study entry. Persistent SGOT (AST), SGPT (ALT), alkaline phosphatase values \> 1.5, or total bilirubin \> 1 times normal upper limits will exclude a subject.
• •17. Active infections (except mild skin and nail fungal infections).
• •18. Acute or chronic pancreatitis.
• •19. Active peptic ulcer disease or gastritis, symptomatic gallstones, or portal hypertension.
• •20. Treatment with any anti-diabetic medication other than insulin within 4 weeks of enrollment.
• •21. Use of any investigational agents within 4 weeks of enrollment.
• •22. Administration of live attenuated vaccine(s) within 2 months of enrollment.
• •23. Any medical condition that, in the opinion of the investigator, will interfere with safe study completion.
• •24. Positive screen for BK viremia at time of screening.
• •25. Untreated hyperlipidemia - TC \> 200 mg/dL, TGC \> 200 mg/dL, LDL \> 130 mg/dL
• •26. Use of glucocorticoids for non-transplant-related indications.