Islet Transplantation in Type 1 Diabetic Patients Using the University of Illinois at Chicago (UIC) Protocol

• Status: Recruiting
• Trial end date: 0000-00-00
• Target enrollment: 1000
• Participant gender: Both

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Illinois at Chicago
• Treatments: Basiliximab; Etanercept; Exenatide; Sirolimus; Tacrolimus
• Last Updated: 2016-12-12

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