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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 September 22, 2014