Islet Transplantation in Type 1 Diabetic Patients Using the University of Illinois at Chicago (UIC) Protocol
Condition: Type 1 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Intervention: Islets of Langerhans transplantation
Intervention description: Each subject may receive 1-3 transplantations of allogeneic human islets of Langerhans and the following medications:
Basiliximab 20 mg iv 2 hours before transplant and 20 mg iv 2 weeks post-transplant; Tacrolimus 1 mg p.o. bid adjusted to reach target trough levels of 3-6 ng/ml; Sirolimus 0.2 mg/kg loading dose, then 0.1 mg/kg p.o. daily adjusted to reach target trough levels of 10-15 ng/ml during the first 3 months post transplant and 7-10 ng/ml thereafter; Etanercept 50 mg iv 1 hour before transplant and 25 mg s.c. on days 3, 7,and 10 post-transplant; Exenatide 5-mcg s.c. bid for 1 week, then 10 mcg bid for 6 months after each transplant
Intervention MeSH terms: Exenatide; Sirolimus; Etanercept; Tacrolimus; Basiliximab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Diabetes Mellitus Type 1; Type 1 Diabetes Mellitus; Islets of Langerhans Transplantation; Allogeneic Islet transplantation

Summary:

      In an earlier Phase 1/2 clinical trial using the Edmonton Protocol of steroid free
      immunosuppression, investigators at University of Illinois at Chicago (UIC) demonstrated the
      safety of islet preparation, iset transplantation, and medical treatment at UIC. Therefore,
      the primary purpose of the present Phase 3 clinical trial is to demonstrate the safety and
      efficacy of allogeneic islet transplantation in improving glycemic control in Type 1 diabetic
      patients using the UIC protocol that was developed and proven effective during the Phase 1/2
      clinical trial.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Type 1 diabetes mellitus for more than 5 years complicated by the following situations
             that persist despite intensive insulin management efforts:

          -  At least one episode of severe hypoglycemia in the past 3 years defined as an event
             with symptoms compatible with hypoglycemia in which the subject required the
             assistance of another person, and which was associated with either a blood glucose
             level <50 mg/dL (2.8 mmol/L) or prompt recovery after oral carbohydrate, intravenous
             glucose, or glucagon administration

          -  Reduced awareness of hypoglycemia, defined by the absence of adequate autonomic
             symptoms at capillary glucose levels of <54 mg/dL (3 mmol/l) as reported by the
             subject

        Exclusion Criteria:

          -  Co-existing cardiac disease: myocardial infarction within the past 6 months,
             angiographic evidence of non-correctable coronary artery disease, ischemia on
             functional cardiac exam, heart failure

          -  Active alcohol or substance abuse, including cigarette smoking (must be abstinent for
             six months)

          -  Psychiatric disorder: schizophrenia, bipolar disorder, or major depression that is
             unstable on medication

          -  History of 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

          -  Family history of MEN2 or MCT

          -  Stroke within the past 6 months

          -  BMI >27 kg/m2

          -  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 75 years

          -  Creatinine clearance <80 mL/min/1.73 m2 by 24-hour urine collection

          -  Serum creatinine consistently >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 >80%

          -  Insulin requirement >0.7 IU/kg/day

          -  HbA1c >12%

          -  Hyperlipidemia (fasting cholesterol >130 mg/dL or fasting triglycerides >200 mg/dL

          -  Medical condition requiring chronic use of steroids

          -  Use of Coumadin or other antiplatelet or anticoagulant therapy, or PT-INR >1.5

          -  Factor V deficiency

          -  Smoking tobacco

          -  Addison's disease

          -  Allergy to radiographic contrast material

          -  Symptomatic cholecystolithiasis

          -  Acute or chronic pancreatitis

          -  Symptomatic peptic ulcer disease

          -  Severe unremitting diarrhea, vomiting, or other gastrointestinal disorders that could
             interfere with medication absorption

          -  Treatment with antidiabetic medication other than insulin within 4 weeks of enrollment

          -  Use of any study medication within 4 weeks of enrollment

          -  Received live attenuated vaccine(s) within 2 months of enrollment

          -  Any medical condition that, in the opinion of the investigator, might interfere with
             safe participation