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Pancreatic Islet Cell Transplantation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00214786
Recruitment Status : Completed
First Posted : September 22, 2005
Results First Posted : June 6, 2014
Last Update Posted : June 14, 2017
Sponsor:
Collaborators:
Baylor Health Care System
University of Miami
Information provided by (Responsible Party):
Baylor Research Institute

Tracking Information
First Submitted Date  ICMJE September 14, 2005
First Posted Date  ICMJE September 22, 2005
Results First Submitted Date  ICMJE February 11, 2013
Results First Posted Date  ICMJE June 6, 2014
Last Update Posted Date June 14, 2017
Study Start Date  ICMJE April 2005
Actual Primary Completion Date July 2007   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 15, 2014)
Achievement of Insulin Independence at 12-month Post Transplant [ Time Frame: 12 months post transplant ]
To assess the number of patients who achieve insulin independence at 12-month after islet cell transplantation
Original Primary Outcome Measures  ICMJE
 (submitted: September 14, 2005)
To assess the achievement of insulin independence at 12-month and 24-month post transplant in patients who undergo pancreatic islet cell transplantation.
Change History Complete list of historical versions of study NCT00214786 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 15, 2014)
  • Presence or Absence of Hypoglycemic Unawareness [ Time Frame: 12 months after transplantation ]
    Number of patients who achieved absence of hypoglycemic unawareness
  • Incidence of Hypoglycemic Episodes [ Time Frame: 12 months after transplantation ]
    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 ]
    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 ]
    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 ]
  • Renal Function [ Time Frame: 12 months after transplantation ]
    Glomerular filtration rate measured by sodium iothalamate I-125 injection (GLOFIL)
  • Morbidity Related to the Immunosuppression Regimen [ Time Frame: 12 months after transplantation ]
    Number of participants who experienced serious adverse events related to immunosuppression regimen
  • Morbidity Related to the Islet Cell Infusion [ Time Frame: 12months after transplantation ]
    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 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 14, 2005)
  • i. Presence or absence of hypoglycemic unawareness
  • ii. To assess incidence of hypoglycemic episodes
  • iii. To assess insulin requirements in patients who did not become insulin independent
  • iv. 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
  • v. To assess the number of islet cell infusions needed to achieve insulin independence
  • vi. To assess renal function
  • vii. To describe morbidity related to the immunosuppression regimen
  • viii. To describe morbidity related to the islet cells infusion
  • ix. To assess the quality of life of the recipients
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pancreatic Islet Cell Transplantation
Official Title  ICMJE Pancreatic Islet Cell Transplantation - A Novel Approach to Immunosuppression and Validation of Remote Site Islet Cell Processing, Islet Cell Culture and Two-Layer Preservation
Brief Summary 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

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Type 1 Diabetes
Intervention  ICMJE Biological: Islet cell transplantation
Allogenic islet transplantation
Study Arms  ICMJE Experimental: Islet Cell Transplantation
Allogenic islet cell transplantation
Intervention: Biological: Islet cell transplantation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 15, 2014)
4
Original Enrollment  ICMJE
 (submitted: September 14, 2005)
15
Actual Study Completion Date  ICMJE July 2007
Actual Primary Completion Date July 2007   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00214786
Other Study ID Numbers  ICMJE 003-040
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Baylor Research Institute
Study Sponsor  ICMJE Baylor Research Institute
Collaborators  ICMJE
  • Baylor Health Care System
  • University of Miami
Investigators  ICMJE
Principal Investigator: Marlon Levy, MD Baylor Regional Transplant Institute
PRS Account Baylor Research Institute
Verification Date June 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP