Cadaveric Islet Transplantation in Patients With Insulin-Dependent Diabetes Mellitus

• Status: Terminated
• Trial end date: 2011-03-01
• Target enrollment: 0
• Participant gender: All

Summary

We hypothesize that the following improvements to islet transplantation will increase the islet mass successfully isolated and allow for engraftment from a single pancreas. The improvements are:

• Using Two-Layer method preservation to improve pancreas quality before islet isolation

• Maintaining isolated islets in culture before transplantation

• Using a steroid-free immunosuppression regimen

• Transplanting the best combination of donor and recipient possible after HLA screening and final crossmatching

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

Details

• Lead Sponsor: University of Nebraska

Criteria

Inclusion Criteria:

• Group 1: Diagnosis of Type-1 diabetes mellitus for more than 5 years with at least one of the following complications:

• Metabolic lability/instability (two or more episodes of severe hypoglycemia) or two or more hospital visits for diabetic ketoacidosis during the previous year

• Progression of secondary complications of diabetes as determined by The Nebraska Medical Center/University of Nebraska Medical Center staff endocrinologists

• Group 2: Diagnosis of Type-1 diabetes with successful renal transplant on steroid-free, FK506/rapamycin-based immunosuppression

Exclusion Criteria:

• Severe co-existing cardiac disease

• Active alcohol or substance abuse, including cigarette smoking

• Psychiatric disorder making the subject not a suitable candidate for transplantation

• History of medical non-compliance

• Active infection, including hepatitis C and B, HIV, and tuberculosis (or suspected tuberculosis)

• Any history of malignancy except squamous or basal cell skin cancer

• BMI >28 kg/meter-squared, or body weight >80kg at screening visit, or >85kg on the day of transplantation (due to the difficulty of obtaining a sufficiently large islet mass to adequately treat either large patients or those whose obesity elevates their insulin needs)

• Positive C-peptide response to intravenous glucose tolerance test and Mixed Meal glucose tolerance test: any C-peptide >0.3 ng/mL post infusion

• Inability to provide informed consent

• Age less than 19 or greater than 70 years

• Creatinine clearance <60 mL/min/1.73 meter-squared for Group 1 and creatinine clearance <40 mL/min/1.73 meter-squared for Group 2 (those subjects currently on immunosuppression due to previous kidney transplant)

• Macroalbuminuria (urinary albumin excretion rate >300 mg/24h) for Group 1 and macroalbuminuria (urinary albumin excretion rate >600mg/24h) for Group 2

• Baseline Hb <10 gm/dL

• Baseline liver function tests outside of normal range

• Presence of gallstones or hemangioma in liver on baseline ultrasound exam

• Positive pregnancy test, intention of future pregnancy, or presently breast-feeding

• Evidence of sensitization on PRA

• Insulin requirement >0.7 IU/kg/day or HbA1c >15%

• Hyperlipidemia

• Under treatment for a medical condition requiring chronic use of steroids

• Use of Coumadin or other anticoagulant therapy (except aspirin) or PT-INR>1.5

• Diagnosis of Addison's disease

Additional Exclusion Criteria for Group 2 Subjects:

• Any history of organ transplantation other than kidney or pancreas

• Any previous graft lost to rejection

• Any history of early, multiple, or vascular renal allograft rejection