Alemtuzumab Induction in Islet Transplantation
- Conditions
- Type 1 Diabetes
- Registration Number
- NCT00175253
- Lead Sponsor
- University of Alberta
- Brief 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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 12
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
University of Alberta - Clinical Islet Transplant Program
🇨🇦Edmonton, Alberta, Canada