Clinical trial NCT00579371: Cadaveric Islet Transplantation in Patients With Insulin-Dependent Diabetes Mellitus
Official title: Cadaveric Islet Transplantation in Patients With Insulin-Dependent Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Islets of Langerhans Transplantation
Diabetes Mellitus, Type 1
Keywords: islet transplantation
type 1 diabetes mellitus
steroid-free immunosuppression
rabbit anti-thymocyte globulin
Lead sponsor: University of Nebraska
Sponsor class: OTHER
First posted: 2007-12-24
Enrollment: 30
Sex: ALL
Minimum age (years): 19
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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 human leukocyte antigens (HLA) screening and final crossmatching

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

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, and transplanting the best combination of donor and recipient possible after HLA screening and final crossmatching.

Eligibility 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 panel reactive antibodies (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 a prothrombin time/international normalized ratio (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

Primary outcomes:
measure: Incidence of insulin independence with a single islet transplant
timeFrame: 1 year post-transplantation
Secondary outcomes:
measure: Islet mass resulting in insulin independence/reduced exogenous insulin requirement
timeFrame: 1 year post-transplantation
measure: Graft survival
timeFrame: 3 years post-transplantation
measure: Metabolic functional assessments of the islet graft
timeFrame: 3 years post-transplantation
Other outcomes:
Locations:
city: Omaha
country: United States
facility: The Nebraska Medical Center
state: Nebraska
Study officials:
affiliation: University of Nebraska
name: R Brian Stevens, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: