Cadaveric Islet Transplantation in Patients With Insulin-Dependent Diabetes Mellitus

Phase 1

Terminated

• Conditions: Islets of Langerhans Transplantation; Diabetes Mellitus, Type 1
• Interventions: Drug: Islets of Langerhans

• Registration Number: NCT00579371
• Lead Sponsor: University of Nebraska

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.

Study Timeline

• Study Start: 2004-03-17
• Study First Submitted: 2007-12-17
• Study First Submitted QC: 2007-12-17
• Study First Posted: 2007-12-24
• Primary Completion: 2011-03
• Study Completion: 2011-03
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-20
• Last Update Posted: 2023-12-21

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 30

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Transplantation of Islets of Langerhans	Islets of Langerhans	Subjects will receive islets isolated from one donor pancreas per transplantation event. Subjects will receive a cumulative dose of 8,000 International Units/kg. Islets will be infused intraportally. If necessary, additional transplantation events will be performed.

Primary Outcome Measures

Name	Time	Method
Incidence of insulin independence with a single islet transplant	1 year post-transplantation	Incidence of insulin independence with a single transplantation measured at one year post-transplantation.

Secondary Outcome Measures

Name	Time	Method
Islet mass resulting in insulin independence/reduced exogenous insulin requirement	1 year post-transplantation	Insulin independence or reduced exogenous insulin required measured at one year post-transplantation.
Graft survival	3 years post-transplantation	The survival of the Islets of Langerhans graft as measured at three years post-transplantation.
Metabolic functional assessments of the islet graft	3 years post-transplantation	An assessment of the metabolic function of the islet of Langerhans graft as measured three years post-transplantation.

Trial Locations

Locations (1)

The Nebraska Medical Center; 🇺🇸 Omaha, Nebraska, United States