Cadaveric Islet Transplantation in Patients With Insulin-Dependent Diabetes Mellitus

December 20, 2023 updated by: University of Nebraska

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

Study Overview

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 Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • The Nebraska Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Transplantation of 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.
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.
Other Names:
  • transplanted islets of Langerhans

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of insulin independence with a single islet transplant
Time Frame: 1 year post-transplantation
Incidence of insulin independence with a single transplantation measured at one year post-transplantation.
1 year post-transplantation

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: R Brian Stevens, MD PhD, University of Nebraska

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 17, 2004

Primary Completion (Actual)

March 1, 2011

Study Completion (Actual)

March 1, 2011

Study Registration Dates

First Submitted

December 17, 2007

First Submitted That Met QC Criteria

December 17, 2007

First Posted (Estimated)

December 24, 2007

Study Record Updates

Last Update Posted (Estimated)

December 21, 2023

Last Update Submitted That Met QC Criteria

December 20, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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