An Open Label, Pilot Investigation, to Assess the Safety and Efficacy of Transplantation of Macro-encapsulated Human Islets Within the Bioartificial Pancreas Beta-Air in Patients With Type 1 Diabetes Mellitus

Exclusion Criteria

• •1. Body mass index (BMI) \> 30 kg/m²
• •2. Insulin requirement of \> 1.0 Units/kg/day
• •3. HbA1c \> 10 % (DCCT)
• •4. Random C-peptide \> 0.003 nmol/l
• •5. Known untreated active proliferative diabetic retinopathy changes or increasing macular oedema
• •6. Renal failure (Glomerular Filtration Rate \<60 ml/min)
• •7. Women of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or unwilling to use adequate contraceptive methods for the duration of the trial (implants, injectables, combined oral contraceptives, hormonal intrauterine device, sexual abstinence or vasectomised partner).
• •8. Active infection including hepatitis B, hepatitis C, HIV, Tbc
• •9. Any history of malignancy except for completely resected squamous or basal cell carcinoma of the skin
• •10. Known active alcohol or drug abuse.
• •11. Any coagulopathy or medical condition that would require long-term anticoagulant therapy (e.g., Warfarin) after transplantation (low-dose aspirin treatment is allowed) or subjects with an international normalized ratio (INR) \> 1.5.
• •12. Severe co-existing cardiac disease, characterized by any of these conditions:
• •1. Recent myocardial infarction (within past 36 weeks)
• •2. Evidence of ischemia on functional cardiac exam within the last year
• •3. Left ventricular ejection fraction \< 30 %
• •4. Cardiovascular conditions within 36 weeks prior to this trial:
• •i. Decompensated heart failure New York Heart Association (NYHA) class III or IV ii. Unstable angina pectoris iii. Coronary arterial bypass graft iv. Coronary angioplasty
• •13. Inadequately treated blood pressure elevation (systolic BP \> 160 mmHg or diastolic blood pressure \> 100 mmHg)
• •14. Use of any medications to treat diabetes other than insulin within 4 weeks of enrolment
• •15. Administration of live attenuated vaccine(s) within 8 weeks of enrolment
• •16. Any previous organ transplant
• •17. Treatment with any immunosuppressive drug
• •18. Any medical condition that, in the opinion of the investigator, will interfere with safe participation in the trial (e.g., systemic glucocorticoids)
• •19. Known or suspected allergy of hypersensitivity to trial product(s) or related products
• •20. The receipt of any investigational product within 30 days of screening for this trial
• •21. Any scheduled transplant in addition to the islet transplantation
• •22. Fulfillment of criteria for clinical pancreas or islet transplantation