Status:

COMPLETED

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

Lead Sponsor:

Diatranz Otsuka Limited

Conditions:

Type 1 Diabetes

Eligibility:

All Genders

35-65 years

Phase:

PHASE1

PHASE2

Brief Summary

The purpose of this study is to establish the safety of xenotransplantation of DIABECELL(R)\[immunoprotected (alginate-encapsulated) porcine islets\] in patients with established type 1 diabetes melli...

Detailed Description

Intraperitoneal islet transplantation has the potential to ameliorate type 1 diabetes mellitus and avert the long-term consequences of chronic diabetes which cannot be achieved by conventional insulin...

Eligibility Criteria

Inclusion

  • 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:
  • 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
  • Previous cerebrovascular disease manifesting as transient ischaemic attacks (TIAs) or stroke
  • Peripheral vascular disease with foot ulcer and/or previous amputation
  • History of New York Heart Association (NYHA) class II, III or IV congestive heart failure (CHF) and/or chronic atrial fibrillation
  • 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
  • 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
  • Haematological disorders, including haemoglobin ≤110 g/L or platelet count \<80 x 109/L
  • Peptic ulcer disease and/or history of previous gastrointestinal bleeding
  • Malignancy other than basal cell carcinoma
  • History of epilepsy
  • Untreated hypothyroidism
  • 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

Exclusion

    Key Trial Info

    Start Date :

    July 1 2009

    Trial Type :

    INTERVENTIONAL

    Allocation :

    ACTUAL

    End Date :

    October 1 2013

    Estimated Enrollment :

    16 Patients enrolled

    Trial Details

    Trial ID

    NCT00940173

    Start Date

    July 1 2009

    End Date

    October 1 2013

    Last Update

    October 20 2017

    Active Locations (1)

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    Centre for Clinical Research and Effective Practice

    Auckland, New Zealand