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
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
The primary objective of this clinical investigation is to investigate the safety of
 implantation of the human islet containing device Beta-Air in type 1 diabetic subjects.

 The secondary objective of this clinical investigation is to investigate if the
 transplantation of macro-encapsulated human islets within the Beta-Air device can provide
 improved glycaemic control in type 1 diabetes patients with reduced incidences of
 hypoglycaemic episodes.
Inclusion Criteria:

 1. Informed consent obtained before any investigation-related activities.
 Investigation-related activities are any procedure that would not have been performed
 during normal management of the subject.

 2. Diagnosis of type 1 diabetes mellitus for > 5 years

 3. Men or women > 18 years of age at the time of enrolment

 4. Involvement in intensive diabetes management defined as self-monitoring of blood
 glucose level no less than a mean of three times per day averaged over each week and
 by the administration of three or more insulin injections per day or insulin pump
 therapy. This management must be under the direction of a diabetologist or diabetes
 specialist during the 12 months prior to study enrolment.

 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