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Pancreatic Islet Cell Transplantation - A Novel Approach to Improve Islet Quality and Engraftment

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Baylor Research Institute
Sponsor:
Collaborator:
Baylor Health Care System
Information provided by (Responsible Party):
Baylor Research Institute
ClinicalTrials.gov Identifier:
NCT00530686
First received: September 13, 2007
Last updated: February 5, 2014
Last verified: February 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
Islet Cell Transplantation
Type 1 Diabetes
Drug: 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 Improve Islet Quality and Engraftment

Resource links provided by NLM:


Further study details as provided by Baylor Research Institute:

Primary Outcome Measures:
  • 1)Presence or absence of hypoglycemic unawareness 2) To assess incidence of hypoglycemic episodes 3) To assess insulin requirements in patients who did not become insulin independent. [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To assess the achievement of insulin independence at 12 month and 24 month post transplant in patients who underwent allo islet cell transplantation. [ Time Frame: 12 months and 24 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 15
Study Start Date: April 2007
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Islet cell transplantation
    The process is based on the enzymatic isolation of the pancreatic islets of Langerhans from an organ procured from a cadaveric donor; the islets obtained are injected into the liver of 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.
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.

Isolation of the islets from donor pancreata will occur in the Baylor University Medical Center Islet Cell Processing Laboratory (ICPL). The islet cell infusion is performed in the Interventional Radiology Suite at Baylor University Medical Center or Baylor All Saints Medical Center by an interventional radiologist. The procedure takes place in a suite designed for invasive procedures using sterile technique with access to general anesthesia if necessary. Following the procedure the patient is observed in the Interventional Radiology recovery area for as long as necessary as determined by a Physician and then transferred to the Transplant Service for an overnight stay. After recovery, the patient is admitted to the hospital on the Transplant Service for a 1-2 day observation.

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.

  Eligibility

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

Inclusion Criteria:

  • 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 24 months
  • Patient is expected to receive an islet cell transplant (up to 3 infusions) for type I diabetes mellitus
  • Type I diabetes mellitus 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 from a diabetology care team
  • Hypoglycemia unawareness, as defined by episodes of loss of cognitive function; or the inability to recognize glucose levels below 50 mg/dL; or frequent episodes of symptomatic hypoglycemia; or admission to the hospital for hypo/hyperglycemic
  • Incapacitating signs and symptoms, as defined by the referring physician
  • HbA1c > 6.5
  • Psychogenically able to comply, in the opinion of the investigator
  • 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:

  • Patient has previously received or is receiving an organ or bone marrow transplant
  • Patient has a known hypersensitivity to Tacrolimus, sirolimus, dacluzimab, or CellCept
  • Patient is pregnant or lactating
  • Patient has participated in a blinded trial or participated in a trial involving a non-marketed (investigational) drug within 3 months of enrollment
  • Patient has participated in a trial involving a marketed drug or an infusion device within 30 days of the start of the trial
  • Glofil or Creatinine Clearance < 60 mL/min
  • Serum Creatinine > 1.6 mg/dL consistently
  • Body mass index > 28
  • Malignancy other than basal cell carcinoma or squamous cell carcinoma
  • Radiographic evidence of pulmonary infection
  • Evidence of liver disease as evidenced by >2X ULN for AST, ALT, Alk Phos., or T bili.
  • Active infections
  • Hypercoagulable states (history of recurrent venous thrombosis, defined thrombophilia)
  • Bleeding / coagulation disorders
  • Basal C-Peptide > 0.3 ng/dL
  • HbA1c > 12%
  • Insulin requirement >0.7 IU/kg/day
  • Seropositivity for HIV, HBV, HCV, HTLV-1
  • Abnormal Pap smear, active gynecological infection
  • Positive exercise or chemical tolerance test
  • Patients currently under treatment for a medical condition requiring chronic use of steroids at a dose of prednisone >5mg/day will be excluded
  • Substance/alcohol abuse
  • Untreated proliferating diabetic retinopathy
  • PPD conversion or positive PPD without INH
  • No Primary care physician or primary care physician less than 6 months
  • Smoking in the last 6 months
  • Abnormal CBC / Hemoglobin < 12 g/dL
  • Macroalbuminuria > 300 mg/24 hours
  • Untreated hyperlipidemia - TC > 200 mg/dL, TGC > 200 mg/dL, LDL > 130 mg/dL
  • Untreated hyponatremia, hypokalemia, hypercalcemia, hypocalcemia
  • Iodine contrast allergy
  • PSA > 4
  • PRA > 20%
  • Active peptic ulcer disease/gallstones/hemangioma
  • 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: NCT00530686

Contacts
Contact: Kerri Purcell, RN, BSN 817-922-4640 KerriP@baylorhealth.edu
Contact: Michelle Acker, RN, CCRC 214-820-6622 MichelCo@baylorhealth.edu

Locations
United States, Texas
Annette C. & Harold C. Simmons Transplant Institute - Baylor University Medical Center, Dallas Texas, USA - Baylor All Saints Medical Center, Fort Worth Texas, USA Recruiting
Dallas, Texas, United States, 75246
Contact: Kerri Purcell, RN, BSN    817-922-4640    kerrip@baylorhealth.edu   
Contact: Michelle Acker, RN,CCRC    214-820-6622    Michelle.Acker@Baylorhealth.edu   
Principal Investigator: Marlon Levy, MD         
Sponsors and Collaborators
Baylor Research Institute
Baylor Health Care System
Investigators
Principal Investigator: Marlon Levy, MD Baylor All Saints
  More Information

No publications provided

Responsible Party: Baylor Research Institute
ClinicalTrials.gov Identifier: NCT00530686     History of Changes
Other Study ID Numbers: Baylor IRB #008-095
Study First Received: September 13, 2007
Last Updated: February 5, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Baylor Research Institute:
Diabetes Mellitus
Hypoglycemia
Hyperglycemia
Type 1 Diabetes
Islet cell transplantation

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

ClinicalTrials.gov processed this record on July 26, 2014