Alemtuzumab Induction in Islet Transplantation

• Status: Completed
• Trial end date: 2012-04-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Alberta
• Collaborator: Juvenile Diabetes Research Foundation
• Treatments: Alemtuzumab

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