Alemtuzumab Induction in Islet Transplantation

This trial is a single-center, prospective, open-label study in 12 Type 1 diabetic participants receiving an islet-alone transplant along with alemtuzumab induction therapy followed by combination tacrolimus and MMF maintenance immunosuppression. Participants will receive 1 to 3 infusions of pancreatic islets of sufficient quantity to attain insulin independence.

The primary objective of this protocol is to assess the safety of a treatment regimen utilizing alemtuzumab induction and a combination of tacrolimus and MMF maintenance immunosuppression in adult Type 1 diabetic participants receiving their first islet transplant.

Inclusion criteria

• open to Canadians only
• participant must have had Type 1 diabetes mellitus for more than 5 years
• diabetes must be complicated by at least 1 of the following situations that persist despite intensive insulin management efforts: (1) Reduced awareness of hypoglycemia, as defined by the absence of adequate autonomic symptoms at plasma glucose levels < 3.0 mmol/L, indicated by, 2 or more episodes of severe hypoglycemia requiring third party assistance within 12 months; or (2) Metabolic instability, characterized by erratic blood glucose levels that interfere with daily activities and or 2 or more hospital visits for diabetic ketoacidosis over the last 12 months.
• Participants must be capable of understanding the purpose and risks of the study and must sign a statement of informed consent.

Exclusion criteria

• Severe co-existing cardiac disease
• Active alcohol or substance abuse, to include cigarette smoking
• Psychiatric disorder making the subject not a suitable candidate for transplantation
• History of non-adherence to prescribed regimens
• Active infection including Hepatitis C, Hepatitis B, HIV, TB
• Any history of or current malignancies except squamous or basal skin cancer
• BMI > 28 kg/m2 at screening visit
• Creatinine clearance < 65 mL/min/1.73 m2
• Blood creatinine > 150 µmol/L (1.7 mg/dL)
• Macroalbuminuria (urinary albumin excretion rate > 300 mg/24h)
• Baseline Hb < 105g/L (<10.5 g/dL) in women, or < 130 g/L (<13 g/dL) in men
• Baseline screening liver function tests outside of normal range
• Untreated proliferative retinopathy
• Positive pregnancy test, intent for future pregnancy or male subjects' intent to procreate, failure to follow effective contraceptive measures, or presently breast feeding
• Previous transplant, or evidence of significant sensitization on PRA
• Insulin requirement >1.0 U/kg/day
• HbA1C >12%
• Uncontrolled hyperlipidemia
• Under treatment for a medical condition requiring chronic use of steroids
• Use of coumadin or other anticoagulant therapy (except aspirin) or subject with PT INR > 1.5
• Untreated Celiac disease
• Patients with Graves disease will be excluded unless previously adequately treated with radioiodine ablative therapy