Cadaveric Islet Transplantation in Patients With Insulin-Dependent Diabetes Mellitus

This study is enrolling participants by invitation only.
Sponsor:
Information provided by:
University of Nebraska
ClinicalTrials.gov Identifier:
NCT00579371
First received: December 17, 2007
Last updated: June 25, 2010
Last verified: June 2010
  Purpose

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

Condition Intervention Phase
Islets of Langerhans Transplantation
Diabetes Mellitus, Type 1
Other: Islets of Langerhans
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Cadaveric Islet Transplantation in Patients With Insulin-Dependent Diabetes Mellitus

Resource links provided by NLM:


Further study details as provided by University of Nebraska:

Primary Outcome Measures:
  • Incidence of insulin independence with a single islet transplant [ Time Frame: 1 year post-transplantation ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Islet mass resulting in insulin independence/reduced exogenous insulin requirement [ Time Frame: 1 year post-transplantation ] [ Designated as safety issue: No ]
  • Graft survival [ Time Frame: 3 years post-transplantation ] [ Designated as safety issue: No ]
  • Metabolic functional assessments of the islet graft [ Time Frame: 3 years post-transplantation ] [ Designated as safety issue: No ]

Estimated Enrollment: 10
Study Start Date: January 2008
Estimated Study Completion Date: January 2013
Estimated Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Other: Islets of Langerhans
Subjects will receive islets isolated from one donor pancreas per transplantation event. Subjects will receive a cumulative dose of 8,000IE/kg. Islets will be infused intraportally. If necessary, additional transplantation events will be performed.

  Eligibility

Ages Eligible for Study:   19 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00579371

Locations
United States, Nebraska
The Nebraska Medical Center
Omaha, Nebraska, United States, 68198
Sponsors and Collaborators
University of Nebraska
Investigators
Principal Investigator: R Brian Stevens, MD PhD University of Nebraska
  More Information

No publications provided

Responsible Party: R Brian Stevens, MD, PhD, University of Nebraska Medical Center
ClinicalTrials.gov Identifier: NCT00579371     History of Changes
Other Study ID Numbers: 149-03-FB, BB IND 11397
Study First Received: December 17, 2007
Last Updated: June 25, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Nebraska:
islet transplantation
type 1 diabetes mellitus
steroid-free immunosuppression
rabbit anti-thymocyte globulin

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on April 17, 2014