Heparinized Islets in Clinical Islet Transplantation

Inclusion Criteria:

Patients must meet all of the following criteria to be considered eligible for participation in the study

• Male and female patients age 18 to 65 years of age.
• Ability to provide written informed consent.
• Mentally stable and able to comply with the procedures of the study protocol.
• Clinical history compatible with type 1 diabetes with onset of disease at < 40 years of age and insulin-dependence for > 5 years at the time of enrolment.
• Absence of stimulated C-peptide <0.1 nmol/L in response to a MMTT.
• All subjects must have received adequate medical treatment of their diabetes under the guidance from an experienced diabetologist.

If not previously kidney transplanted the patient must also have;

• At least one episode of severe hypoglycemia in the past 1 year defined as an event with at least one of the following symptoms; memory loss, confusion, uncontrollable behavior, unusual difficulty in awakening, suspected seizure, loss of consciousness, or visual symptoms, in which the subject was unable to treat him/herself and which was associated with either a blood/plasma glucose level < 54 mg/dl [3.0 mmol/L] or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration

and

• Reduced awareness of hypoglycemia as defined by a Clarke score of 4 or more.

Exclusion Criteria:

Patients who meet any of these criteria are not eligible for participation in the study:

• Patients with prior organ transplants other than a well functioning kidney graft
• Patients with body mass index (BMI) > 30.
• Insulin requirement > 1 Unit/kg/day.
• Consistently abnormal liver function tests ( > 1.5 x the upper limit of normal on two consecutive measurements > 2 weeks apart)
• Unstable diabetic retinopathy
• Hypercoagulability disorder or coagulopathy or INR>1.5
• Any history of malignancy except for completely resected squamous or basal cell carcinoma of the skin
• Patients with unstable cardiovascular status
• Patients with active infections, unless treatment is not judged necessary by the investigators
• Patients with serological evidence of infection with HIV, hepatitis B (patients with serology consistent with previous vaccination and a history of vaccination are acceptable) or hepatitis C.
• Patients with active peptic ulcer disease, symptomatic gallstones or portal hypertension.
• Patients who are pregnant or breastfeeding, or who intend to become pregnant.
• Sexually-active females who are not: a) post-menopausal, b) surgically sterile, or c) using an acceptable method of contraception: oral contraceptives, Norplant, Depo-Provera, and barrier devices combined with spermicidal gel are acceptable; condoms used alone are not acceptable
• Active alcohol or substance abuse
• Patients with evidence of high-level sensitization (PRA> 20%).
• Patients with psychological conditions that make it unsafe to undergo islet transplantation or which preclude compliance with prescribed therapy
• Activated Protein C Resistance (APC-R)
• HbA1c >10% (Swedish standard).
• Allergy to eggs
• Antibodies against Avidin
• Patients with any condition or any circumstance that in the opinion of the investigator would make it unsafe to undergo an islet transplant