Islet Transplantation in Type 1 Diabetic Patients Using the Edmonton Protocol of Steroid Free Immunosuppression
Diabetes Mellitus, Type 1
About this trial
This is an interventional treatment trial for Diabetes Mellitus, Type 1 focused on measuring Diabetes Mellitus, Type 1, Islets of Langerhans Transplantation, Exenatide, Soluble tumor necrosis factor receptor
Eligibility Criteria
Inclusion Criteria:
Type 1 diabetes > 5 years complicated by at least one of the following situations despite intensive insulin management:
- Reduced awareness of hypoglycemia at plasma glucose levels < 54 mg/dL
- Metabolic lability/instability characterized by two or more episodes of severe hypoglycemia or hospital visits for diabetic ketoacidosis over the last year
Progressive secondary complications of diabetes:
- Retinopathy-three step progression using the ETDRS grading system or equivalent progression;
- Nephropathy- microalbuminuria rise of 50 µg/min (72 mg/24h) over three months within the past two years despite using an ACE inhibitor;
- Neuropathy-persistent gastroparesis, postural hypotension, neuropathic bowel or bladder, or severe peripheral neuropathy unresponsive to management
Exclusion Criteria:
Co-existing cardiac disease:
- Myocardial infarction within past six months
- Angiographic evidence of non-correctable coronary artery disease
- Ischemia on functional cardiac exam d. Heart failure > NYHA II
- Active alcohol or substance abuse or cigarette smoking
- Psychiatric disorder: schizophrenia, bipolar disorder, or major depression that is unstable on medication
- Non-adherence to prescribed regimens
- Active infection including hepatitis C, hepatitis B, HIV
- TB by history, current infection, or under treatment for suspected TB
- History of malignancies except squamous or basal skin cancer
- Stroke within the past 6 months
- BMI > 26 kg/m2 or body weight > 70 kg at screening visit
- C-peptide response to glucagon stimulation, any C-peptide ≥ 0.3 ng/mL
- Inability to provide informed consent
- Age less than 18 or greater than 65 years
- Creatinine clearance < 85 mL/min/1.73 m2 by 24-hour urine collection
- Serum creatinine > 1.5 mg/dL
- Macroalbuminuria > 300 mg/24h
- Baseline Hb < 12 gm/dL in women, < 13 gm/dL in men
- Baseline liver function tests outside normal range
- Untreated proliferative retinopathy
- Positive pregnancy test, intent for pregnancy, male's intent to procreate, unwilling to use effective contraception, breast-feeding
- Previous transplant or PRA reactivity > 20%)
- Insulin requirement > 0.7 IU/kg/day
- HbA1C > 12%
- Hyperlipidemia
- Chronic use of steroids
- Use of coumadin or other anticoagulant (except aspirin) or PT INR > 1.5
- Addison's disease
- Allergy to radiographic contrast material
Sites / Locations
- University of Illinois at Chicago
Arms of the Study
Arm 1
Arm 2
Active Comparator
Active Comparator
Group 1 (Islet Cell Transplant)
Group 2 (Islet Cell Transplant plus)
1-3 Islet transplants by the Edmonton Protocol of Steroid Free Immunosuppression using daclizumab 1 mg/kg IV immediately pre-transplant and 2, 4, 6, and 8 weeks after transplant; sirolimus dosed to maintain serum trough levels 12-15 ng/mL for three months post-transplant and 7-10 ng/mL therafter; tacrolimus dosed to maintain serum trough levels 3-6 ng/mL throughout the study.
1-3 islet transplants by the Edmonton Protocol of Steroid Free Immunosuppression using daclizumab 1 mg/kg IV immediately pre-transplant and 2, 4, 6, and 8 weeks after transplant; sirolimus dosed to maintain serum trough levels 12-15 ng/mL for 3 months post-transplant and 7-10 mg/mL thereafter; tacrolimus dosed to serum trough levels 3-6 ng/mL throughout the study; etanercept 50 mg IV pre-transplant, 25 mg subcutaneously post-transplant Days 3, 7, 10; exenatide 5-mcg subcutaneously twice daily for I week, then up to 10-mcg twice daily for 6 months after the last islet transplant.