Pancreatic Islet Cell Transplantation
|Study Design:||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|
- Achievement of Insulin Independence at 12-month Post Transplant [ Time Frame: 12 months post transplant ] [ Designated as safety issue: No ]To assess the number of patients who achieve insulin independence at 12-month after islet cell transplantation
- Presence or Absence of Hypoglycemic Unawareness [ Time Frame: 12 months after transplantation ] [ Designated as safety issue: No ]Number of patients who achieved absence of hypoglycemic unawareness
- Incidence of Hypoglycemic Episodes [ Time Frame: 12 months after transplantation ] [ Designated as safety issue: No ]Blood glucose <70 mg/dl, number of times reported per month
- Change of Insulin Requirements in Patients Who Did Not Become Insulin Independent [ Time Frame: 12 months after transplantation ] [ Designated as safety issue: No ]Percentage of insulin requirement at month 12 against that at baseline in the patients who did not achieve insulin independence. The percentage less than 100% indicates that subjects reduced insulin requirements 12 months after islet transplantation when compared with those at pre-transplant, while the parentage more than 100% represents that patients needed higher amount of exogenous insulin 12 months after islet transplantation.
- Islet Cell Mass Obtained After Remote Site Processing [ Time Frame: At transplantation ] [ Designated as safety issue: No ]The sum of Islet mass obtained after transport using the two-layer preservation method, remote site processing and islet culture. Islet mass as defined by Islet Equivalent per kilogram recipient body weight.
- The Number of Islet Cell Infusions Needed to Achieve Insulin Independence [ Time Frame: 12 months after transplantation ] [ Designated as safety issue: No ]
- Renal Function [ Time Frame: 12 months after transplantation ] [ Designated as safety issue: Yes ]Glomerular filtration rate measured by sodium iothalamate I-125 injection (GLOFIL)
- Morbidity Related to the Immunosuppression Regimen [ Time Frame: 12 months after transplantation ] [ Designated as safety issue: Yes ]Number of participants who experienced serious adverse events related to immunosuppression regimen
- Morbidity Related to the Islet Cell Infusion [ Time Frame: 12months after transplantation ] [ Designated as safety issue: Yes ]Number of participants who experienced serious adverse events related to islet cell infusion
- The Quality of Life of the Recipients Measured With the RAND 36-item Short Form Health Survey [ Time Frame: 12 months after transplantation ] [ Designated as safety issue: No ]Averaged score in subscales of 'physical functioning', 'Role limitations due to emotional problems', 'energy/fatigue', 'emotional well-being', 'social functioning', 'pain' and 'general health' in the RAND 36-item short form health survey (SF-36). Full scale range is 0-100 for all subscales with 100 as the best outcome and 0 as the worst outcome.
|Study Start Date:||April 2005|
|Study Completion Date:||July 2007|
|Primary Completion Date:||July 2007 (Final data collection date for primary outcome measure)|
Experimental: Islet Cell Transplantation
Allogenic islet cell transplantation
Biological: Islet cell transplantation
Allogenic islet transplantation
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00214786
|United States, Texas|
|Baylor Regional Transplant Institute - Baylor University Medical Center|
|Dallas, Texas, United States, 75246|
|Principal Investigator:||Marlon Levy, MD||Baylor Regional Transplant Institute|