Islet Transplantation Using Campath-1H and Infliximab Induction
Islet Transplantation Using Campath-1H and Infliximab Induction
Islet transplantation has been investigated as a treatment for Type 1 diabetes mellitus in
 selected patients with inadequate glucose control despite insulin therapy. However, the
 perennial hope that such an approach would result in long-term freedom from the need for
 exogenous insulin, with stabilization of the secondary complications of diabetes, has failed
 to materialize in practice. The goal of the present study is therefore to improve the safety
 and efficacy of clinical islet-alone transplantation by minimizing dependence on
 calcineurin-inhibitor therapy - thereby avoiding potential nephrotoxicity, and furthermore
 improving success with single-donor islet infusions by avoiding all diabetogenic
 immunosuppression. Campath-1H, combined with Infliximab induction therapy provides a unique
 opportunity to minimize dosing of maintenance long-term immunosuppression while further
 promoting islet engraftment.
This is a single-centre, prospective, open-label study in Type 1 diabetic participants
 receiving an islet cell transplant; all participants will receive Campath-1H + Infliximab
 induction therapy followed by sirolimus and ultra-low dose tacrolimus maintenance therapy.

 The primary objective of this protocol is to assess the safety of this treatment regimen in
 adult Type 1 diabetic participants receiving their first islet transplant.
Inclusion Criteria:

 -  must have Type 1 diabetes mellitus for more than 5 years

 -  diabetes must be complicated by at least one of the following situations that persist
 despite intensive insulin management efforts. The complicating situations are (1)
 Reduced awareness of hypoglycemia, as defined by the absence of adequate autonomic
 symptoms at plasma glucose levels of < 3.0 mmol/L; (2) Metabolic lability/instability,
 characterized by MAGE ≥ 11.0 mmol/L and wide swings in blood glucose despite optimal
 diabetes therapy; and (3) Despite efforts at optimal glucose control, progressive
 secondary complications of diabetes, including retinopathy, neuropathy, or nephropathy

 Exclusion Criteria:

 -  Severe co-existing cardiac disease

 -  Active alcohol or substance abuse

 -  Psychiatric disorder making the subject not a suitable candidate for transplantation

 -  Active infection including hepatitis C, hepatitis B, HIV, or TB

 -  Any history of or current malignancies except squamous or basal skin cancer

 -  BMI > 28 kg/m2 or body weight > 85 kg at screening visit

 -  Positive fasting C-peptide response on assessment (2 positive results)

 -  Creatinine clearance < 80 mL/min/1.73 m2

 -  Serum creatinine > 150 µmol/L

 -  Macroalbuminuria (urinary albumin excretion rate > 300 mg/24h)

 -  Baseline Hb < 105g/L in women, or < 130 g/L in men

 -  Baseline LFT's 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 sensitization on PRA

 -  Insulin requirement > 1.0 IU/kg/day

 -  HbA1C > 0.12

 -  Hyperlipidemia (fasting LDL cholesterol > 3.4 mmol/L, treated or untreated; and/or
 fasting triglycerides > 2.3 mmol/L)

 -  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 Addison's disease

 -  Untreated Celiac disease

 -  Untreated thyroid disease