Pancreatic Islet Cell Transplantation

This study has been completed.
Sponsor:
Collaborators:
Baylor Health Care System
University of Miami
Information provided by (Responsible Party):
Baylor Research Institute
ClinicalTrials.gov Identifier:
NCT00214786
First received: September 14, 2005
Last updated: May 15, 2014
Last verified: May 2014
  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
Type 1 Diabetes
Biological: Islet cell transplantation
Phase 1

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Baylor Research Institute:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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.


Enrollment: 4
Study Start Date: April 2005
Study Completion Date: July 2007
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Islet Cell Transplantation
Allogenic islet cell transplantation
Biological: Islet cell transplantation
Allogenic islet transplantation

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 Institutional Review Board (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, daclizumab, 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. Glomerular filtration rate (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 Human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), Human T-cell leukemia virus-1 (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) Purified protein derivative (PPD) conversion or positive PPD without isonicotinic acid hydrazide (INH) bb) No Primary care physician or primary care physician less than 6 months cc) Smoking in the last 6 months dd) Abnormal Complete Blood Count (CBC) / Hemoglobin < 12 g/dL ee) Macroalbuminuria > 300 mg/24 hours ff) History of thyroid disease other than autoimmune disease gg) Untreated hyperlipidemia - Total Cholesterol (TC) > 240 mg/dL, Triglycerides (TGC) > 200 mg/dL, Low Density Lipoprotein (LDL) > 140 mg/dL hh) Untreated hyponatremia, hypokalemia, hypercalcemia, hypocalcemia ii) Iodine contrast allergy jj) Prostate Specific Antigen (PSA) > 4 kk) Panel Reactive Antibody (PRA) > 20% ll) Active peptic ulcer disease/gallstones/hemangioma mm) Abnormal mammogram
  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: 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 Health Care System
University of Miami
Investigators
Principal Investigator: Marlon Levy, MD Baylor Regional Transplant Institute
  More Information

No publications provided

Responsible Party: Baylor Research Institute
ClinicalTrials.gov Identifier: NCT00214786     History of Changes
Other Study ID Numbers: Baylor IRB #003-040
Study First Received: September 14, 2005
Results First Received: February 11, 2013
Last Updated: May 15, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Baylor Research Institute:
Diabetes Mellitus
Hypoglycemia
Hyperglycemia

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

ClinicalTrials.gov processed this record on October 23, 2014