Islet Transplantation in Type 1 Diabetic Patients Using the Edmonton Protocol of Steroid Free Immunosuppression

• Status: Completed
• Trial end date: 2020-07-15
• Target enrollment: 0
• Participant gender: All

Summary

The primary purpose of this study is to demonstrate the safety of allogeneic islet transplantation in type 1 diabetic patients performed at the University of Illinois at Chicago (UIC). The purpose is to reproduce the Edmonton protocol to demonstrate that pancreatic islets isolated at UIC are safe and of sufficient quality to provide reproducible graft function.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Illinois at Chicago
• Treatments: Etanercept; Exenatide

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