Open-label Investigation of the Safety and Effectiveness of DIABECELL(R) in Patients With Type I Diabetes Mellitus

This is an interventional treatment trial for Type 1 Diabetes focused on measuring xenotransplantation, type I diabetes, porcine islets Read More

Inclusion criteria:

• Adults (males or females) in the age range 35 to 65 years
• Diagnosis of type 1 diabetes mellitus (minimum duration of 5 years) in accordance with the American Diabetes Association's criteria. Patients should have been treated continuously with insulin since diagnosis (Expert Committee on the Diagnosis and Classification of Diabetes Mellitus 2002)
• Patients with established brittle type I diabetes mellitus with a well-documented chronic history of severe metabolic instability who cannot achieve acceptable metabolic control without experiencing multiple episodes of severe hypoglycaemia, often with unawareness; or
• with degrees of hypoglycaemia, who cannot be adequately managed with intensive insulin therapy alone despite intensive diabetes management delivered by a qualified diabetes team for at least six months prior to enrolment
• Patients should have an HbA1C ≥7% and ≤10% calculated as the average of the last four consecutive HbA1C readings during the 8-week baseline run-in period. The difference between the highest and lowest of the four HbA1C reading should be no more than 0.5%.
• Plasma C-peptide <0.2 ng/ml following a glucagon stimulation test (Scheen et al. 1996)
• If female, no childbearing capability (those who are more than 2 years postmenopausal or have undergone voluntary sterilisation can be considered for enrolment)
• Provision of written informed consent. Patients will be required to agree to comply with all tests and visits specified in the protocol, and they (and their partners/close contacts) will also be required to consent to long-term microbiological monitoring, which is an integral part of the study

Exclusion criteria:

• Type 2 diabetes, defined as age of onset >30 years and/or a history of treatment with oral hypoglycaemic medications and/or insulin resistance (defined as an insulin dose requirement ≥1.2 U/kg/day)
• An average HbA1C < 7% and >10% during the 8-week baseline run-in period
• Body mass index (BMI) ≥30 kg/m2 or ≤20 kg/m2
• Active infection, with plasma C-reactive protein ≥10 mg/L at baseline
• Previous receipt of an organ, skin graft, or other tissue transplant from a human or animal donor
• Treatment with immunosuppressive medications for another medical condition
• Previous history of peritoneal disease or abnormal findings at baseline laparoscopy
• Previous abdominal surgery, excluding uncomplicated appendectomy or cholecystectomy
• History of pelvic inflammatory disease or endometriosis
• Inability to tolerate oral medications or a history of significant malabsorption
• HIV antibody and/or risk factors for HIV infection
• Positive hepatitis C antibody, positive hepatitis B surface antigen, and hepatitis B core antibody
• Kidney disease, defined as serum creatinine >130 μmol/L in men and >110 μmol/L in women and/or urinary albumin >300 mg/L and/or haematuria and/or active urinary sediment or casts
• Diabetes microvascular complications defined as untreated, potentially vision-threatening proliferative or pre-proliferative retinopathy or maculopathy; painful peripheral neuropathy; autonomic neuropathy manifesting as postural hypotension; gastroparesis or diabetic enteropathy
• Diagnosis of coeliac disease and history of gastrointestinal symptoms including chronic or recurrent diarrhoea, malabsorption, weight loss, and abdominal distension or bloating on exposure to gluten products in the diet

• Serious comorbid conditions that are likely to affect participation in the study, including:

  1. Previous coronary heart disease manifesting as non-ST elevation myocardial infarction (NSTEMI), Q-wave infarction or unstable angina; coronary artery bypass graft (CABG); or percutaneous angioplasty
  2. Previous cerebrovascular disease manifesting as transient ischaemic attacks (TIAs) or stroke
  3. Peripheral vascular disease with foot ulcer and/or previous amputation
  4. History of New York Heart Association (NYHA) class II, III or IV congestive heart failure (CHF) and/or chronic atrial fibrillation
  5. Chronic obstructive pulmonary disease (COPD) or asthma with previous hospitalisation for decompensation; a requirement for mechanical ventilation at any stage; or long-term treatment with oral corticosteroids
  6. Liver disease with abnormal liver function tests defined as serum bilirubin ≥20 µmol/L, and/or ALT ≥100 U/L, and/or GGT ≥100 U/L, and/or albumin <35 g/L
  7. Haematological disorders, including haemoglobin ≤110 g/L or platelet count <80 x 109/L
  8. Peptic ulcer disease and/or history of previous gastrointestinal bleeding
  9. Malignancy other than basal cell carcinoma
  10. History of epilepsy
  11. Untreated hypothyroidism
  12. Known adrenal insufficiency
• History of drug, substance or alcohol abuse
• Current oestrogen (e.g. cortisol) therapy
• Any factor detected from psychometric evaluation at Visit 2 Pre-Tx during the screening period which may in the opinion of the Clinical Psychologist affect an individual's ability to fully participate in the study
• Any other condition that, in the opinion of the Investigator, may interfere with adherence to the study protocol, including dementia, mental illness, or a history of non-adherence to appointments or treatments