alemtuzumab induction in islet transplantation

Conditions: Type 1 Diabetes

Summary: our experience suggests that further research with alemtuzumab is attractive in islet transplantation. therefore, in this study we propose to combine alemtuzumab induction pre-transplant, with tacrolimus and mycophenolate mofetil maintenance immunosuppression post-transplant. in the critical early phase post transplant, we anticipate that this regimen will prove to be more effective in control of autoimmunity or rejection events, and have a more desirable side-effect profile, than previously tested combinations of induction and immunosuppressive agents.

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.

Eligibility criteria:
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

Keywords: islet transplantation