Pancreatic Islet Cell Transplantation

This study has been completed.
Sponsor:
Collaborators:
Baylor University
Diabetes Research Institute, Miami, Florida
Information provided by:
Baylor Research Institute
ClinicalTrials.gov Identifier:
NCT00214786
First received: September 14, 2005
Last updated: August 28, 2008
Last verified: August 2008
  Purpose

The purpose of this study is to assess a novel approach to immunosuppression in allogenic pancreatic islet cell transplant recipients. In addition, the study aims to assess remote site islet processing with culture for pancreatic islet cell transplantation in human subjects.


Condition Intervention Phase
Islet Cell Transplantation
Procedure: Islet cell transplantation
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pancreatic Islet Cell Transplantation - A Novel Approach to Immunosuppression and Validation of Remote Site Islet Cell Processing, Islet Cell Culture and Two-Layer Preservation

Resource links provided by NLM:


Further study details as provided by Baylor Research Institute:

Primary Outcome Measures:
  • To assess the achievement of insulin independence at 12-month and 24-month post transplant in patients who undergo pancreatic islet cell transplantation.

Secondary Outcome Measures:
  • Presence or absence of hypoglycemic unawareness
  • To assess incidence of hypoglycemic episodes
  • To assess insulin requirements in patients who did not become insulin independent
  • To assess the islet cell mass, its viability and function obtained after transport using the two-layer preservation method, remote site processing and islet culture
  • To assess the number of islet cell infusions needed to achieve insulin independence
  • To assess renal function
  • To describe morbidity related to the immunosuppression regimen
  • To describe morbidity related to the islet cells infusion
  • To assess the quality of life of the recipients

Estimated Enrollment: 15
Study Start Date: April 2005
Detailed Description:

The purpose of this study is to assess a novel approach to immunosuppression in allogenic pancreatic islet cell transplant recipients. In addition, the study aims to assess remote site islet processing with culture for pancreatic islet cell transplantation in human subjects.

Detailed Description: Diabetes mellitus (DM) type I is a disease that has significant social and economical impact. The prevalence of the disease in the United States is about 120,000 in individuals aged 19 or less and 300,000 to 500,000 at all ages and 150 million worldwide.

So far there are no mechanical devices able to effectively adjust the dose of insulin injected according to the serum glucose in patients with DM. This leads to less than perfect sugar control, with episodes of hypoglycemia. Successful pancreas transplantation averts the need of insulin administration.

The emerging alternative to whole organ pancreas transplantation is pancreatic islet cell transplantation (ICT). The process is based on the enzymatic isolation of the pancreatic islets from an organ procured from a cadaver donor. The islets obtained are injected into the liver in the recipient via percutaneous catheterization of the portal venous system. This procedure allows the selective transplantation of the insulin-producing cell population avoiding open surgery as well as the transplantation of the duodenum and the exocrine pancreas and their related morbidity.

The initial efforts with ICT had only modest results. The immunosuppression regimen was similar to the one used in solid organ transplantation, based on high dose steroids and calcineurin inhibitors - both agents with diabetogenic effects. The results improved markedly with the changes in the manipulations of the islets, and the change in immunosuppression thus avoiding the higher doses of steroids and using sirolimus, tacrolimus and daclizumab initiated by the investigators group at the University of Alberta in Edmonton, Canada. Their protocol requires in general two islet cell infusions in order to attain the critical cell mass necessary to achieve insulin-independency. The changes in treatment were adopted as the Edmonton Protocol, which is used in several transplant centers, worldwide.

A novel approach to organ preservation uses the two-layer preservation technique. This allows for longer travel time for the eventual shipment of the pancreas to an islet cell processing facility remotely located from the donor procurement site.

The isolation of the islets from the donor pancreas will be performed at the Diabetes Research Institute in Miami, Florida, according to the standard currently used by that institution. The Diabetes Research Institute is a well-established center with a state-of-the-art islet cell isolation facility for the purpose of transplantation in humans, accredited and monitored by the FDA according to FDA standards.

The focus of the research in the ICT is centered on the development of a safe and effective procedure that will eventually replace surgical pancreas transplantation together with an ideal immunosuppressive regimen that provides safe and effective prevention against rejection, while minimizing the adverse events associated that negatively impact transplant recipient's quality of life.

This study is being conducted as a validation of the Edmonton protocol for ICT at our institution. Our aim is to test the efficacy of the use of the two-layer preservation technique for transport of the donor pancreas to the off-site processing facility and the use of islet cell culture in the off-site processing facility before the islet isolate is shipped to our center.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patient has been fully informed and has signed an IRB approved informed consent form and is willing and able to follow study procedures for the full 2 years
  2. Patient is expected to receive an islet cell transplant (up to 3 infusions) for type I diabetes mellitus

    • Type I diabetes of more than 5 years duration
    • Age between 18 and 65
    • Unstable diabetes mellitus control, as defined by glucose measurements above 200 mg/dL and/or below 80 mg/dL despite adequate medical care
    • Hypoglycemia unawareness, as defined by episodes of loss of cognitive function
    • Incapacitating signs and symptoms, as defined by the referring physician
    • Poor control of HbA1c > 8%
    • Psychogenically able to comply, in the opinion of the investigator
  3. Female patients of childbearing potential must have a negative urine or serum pregnancy test upon hospitalization or within 7 days prior to enrollment and have agreed to utilize effective birth control throughout the study as well as for 6 weeks following study completion.

Exclusion Criteria:

Patients meeting any of the following criteria will be excluded from study participation.

  1. Patient has previously received or is receiving an organ or bone marrow transplant
  2. Patient has a known hypersensitivity to Tacrolimus, sirolimus, dacluzimab, or CellCept
  3. Patient is pregnant or lactating
  4. Patient has participated in a blinded trial or participated in a trial involving a non-marketed (investigational) drug within 3 months of enrollment
  5. Patient has participated in a trial involving a marketed drug or an infusion device within 30 days of the start of the trial
  6. Glofil < 60 mL/min
  7. Serum Creatinine > 1.6 mg/dL consistently
  8. Body mass index > 30
  9. Autoimmune thyroiditis
  10. Malignancy other than basal cell carcinoma or squamous cell carcinoma
  11. Radiographic evidence of pulmonary infection
  12. Evidence of liver disease
  13. Portal hypertension
  14. Active infections
  15. Hypercoagulable states (history of recurrent venous thrombosis, defined thrombophilia)
  16. Bleeding / coagulation disorders
  17. Basal insulin C-Peptide > 0.3 ng/dL
  18. Insulin C-peptide > 0.3 ng/dL during stimulation test
  19. HbA1c > 12%
  20. Insulin requirement > 1 IU/kg/day
  21. Seropositivity for HIV, HBV, HCV, HTLV-1
  22. Abnormal Pap smear in the last two months, active gynecological infection
  23. Positive exercise or chemical tolerance test
  24. Steroid dependence
  25. Substance/alcohol abuse
  26. Untreated proliferating diabetic retinopathy aa) PPD conversion or positive PPD without INH bb) No Primary care physician or primary care physician less than 6 months cc) Smoking in the last 6 months dd) Abnormal CBC / Hemoglobin < 12 g/dL ee) Macroalbuminuria > 300 mg/24 hours ff) History of thyroid disease other than autoimmune disease gg) Untreated hyperlipidemia - TC > 240 mg/dL, TGC > 200 mg/dL, LDL > 140 mg/dL hh) Untreated hyponatremia, hypokalemia, hypercalcemia, hypocalcemia ii) Iodine contrast allergy jj) PSA > 4 kk) PRA > 20% ll) Active peptic ulcer disease/gallstones/hemangoima mm) Abnormal mammogram
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00214786

Locations
United States, Texas
Baylor Regional Transplant Institute - Baylor University Medical Center
Dallas, Texas, United States, 75246
Sponsors and Collaborators
Baylor Research Institute
Baylor University
Diabetes Research Institute, Miami, Florida
Investigators
Principal Investigator: Marlon Levy, MD Baylor Regional Transplant Institute
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00214786     History of Changes
Other Study ID Numbers: Baylor IRB #003-040
Study First Received: September 14, 2005
Last Updated: August 28, 2008
Health Authority: United States: Food and Drug Administration

Keywords provided by Baylor Research Institute:
Diabetes Mellitus
Hypoglycemia
Hyperglycemia

ClinicalTrials.gov processed this record on April 16, 2014