Clinical Islet Transplantation Using the Edmonton Protocol

This study has been withdrawn prior to enrollment.
(no funding)
Sponsor:
Collaborator:
London Health Sciences Centre
Information provided by:
Lawson Health Research Institute
ClinicalTrials.gov Identifier:
NCT00309231
First received: March 29, 2006
Last updated: June 8, 2010
Last verified: June 2010
  Purpose

The purpose of this study is to perform a series of islet transplants using the Edmonton protocol. Patients with Type I Diabetes and glycemic lability, severe hypoglycemia or hypoglycemic unawareness will undergo transplantation of purified pancreatic islets from cadaveric donors into the portal vein, followed by steroid-free immunosuppression as per the Edmonton protocol (IL-2 antibody induction, sirolimus, low dose tacrolimus-based immunosuppression). The goals of the transplant are to improve glycemic control, stabilize blood sugars and achieve insulin independence.


Condition Intervention Phase
Type 1 Diabetes
Procedure: Islet Allotransplantation
Phase 3

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Clinical Islet Transplantation Using the Edmonton Protocol

Resource links provided by NLM:


Further study details as provided by Lawson Health Research Institute:

Estimated Enrollment: 8
Estimated Study Completion Date: January 2008
Intervention Details:
    Procedure: Islet Allotransplantation
    Clinical islet transplantation using the Edmonton protocol, steroid free immunosuppression using sirolimus and tacrolimus and basilixumab induction therapy
Detailed Description:

The purpose of this study is to document the outcomes of islet transplant at our centre while replicating the Edmonton protocol. The Edmonton protocol, as described above, is currently the standard clinical protocol for conducting clinical islet transplantation in selected patients with type 1 diabetes. We propose to conduct a feasibility study to document the availability and frequency of donor organs, test the process of islet isolation, assess the implementation of procedures to transplant islets and administer immunosuppression, monitor the complications of immunosuppression and document the success and safety of the transplant procedure at our centre.

The outcomes we propose to document include: 1) the number of patients who achieve insulin independence one year after completing the Edmonton protocol 2) the A1c value one year after completing the Edmonton protocol 3) graft survival as measured by basal and stimulated C-peptide levels 4) islet equivalents isolated from each donor organ and islet equivalents per kg transplanted 5) complications of islet transplant and immunosuppressive therapy.

Eight patients who have had type 1 diabetes for more than 5 years will undergo islet allotransplantation using the Edmonton protocol. It is expected that most patients will require a minimum of two transplant procedures to receive enough islets to achieve insulin independence. Procedures will follow published guidelines.

Pancreata will be isolated from brain-dead donors according to published protocols, including the two-layer cold storage method. Islets will be cultured for up to 48 hours to facilitate timing of the islet infusion.

Islets will be infused into the portal vein. Post transplant immunosuppression will consist of the modified Edmonton protocol as outlined by Ryan et al including basiliximab induction therapy, sirolimus and tacrolimus maintenance therapy, aspirin and enoxaparin thromboprophylaxis, pneumocystis carinii prophylaxis with sulfamethoxazole/trimethoprim for 6 months and cytomegalovirus prophylaxis for 3 months if indicated. Insulin requirements will be monitored closely after transplant. Serum glucose, glycosylated haemoglobin, serum C-peptide, creatinine, and lipid concentrations will be monitored.

Patients will be seen in follow up every month initially and longer term every 3 to 6 months as required. Glucose control, immunosuppressive levels and adverse events will be monitored regularly. Patients will be monitored for complications of diabetes as per standard guidelines. Tests of beta cell function (mixed meal Ensure test for glucose and C-peptide) will be performed every 3 months initially and then every 6 months once stable.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients with type 1 diabetes of at least 5 years duration, with either severe hypoglycemia with unawareness, or severe glycemic lability

Criteria

Inclusion Criteria:

  • age 18-65 years
  • type 1 diabetes for at least 5 years
  • at least 1 of the following: a) frequent, severe hypoglycaemia b) hypoglycemic unawareness* c) glycemic lability despite an optimal insulin regimen*, and failure of intensive insulin therapy as judged by independent endocrinologist

Exclusion Criteria:

  • obesity (BMI >28
  • insulin requirements > 0.7 U/kg/day
  • history of cancer (except basal or squamous skin cancer)
  • unstable, severe, or non-correctable cardiac disease
  • previous organ transplant
  • evidence of sensitization (PRA>20%)
  • renal dysfunction (macroalbuminuria, renal dialysis)
  • untreated proliferative retinopathy
  • active infection, including hep C, hep B, HIV, TB
  • current cigarette smoking (6 months abstinence required) or substance abuse
  • indication for steroid medications (exception steroid inhalers, topical steroids)
  • indication for anticoagulation (exception aspirin)
  • pregnancy or desire for future pregnancy; breast-feeding
  • major psychiatric illness
  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: NCT00309231

Locations
Canada, Ontario
London Health Sciences Centre University Campus
London, Ontario, Canada, N6A 4L6
Sponsors and Collaborators
Lawson Health Research Institute
London Health Sciences Centre
Investigators
Principal Investigator: William Wall, MD University of Western Ontario, Canada
  More Information

Publications:
Responsible Party: Dr. William Wall, Lawson Health Research Institute
ClinicalTrials.gov Identifier: NCT00309231     History of Changes
Other Study ID Numbers: R-05-873, 11898
Study First Received: March 29, 2006
Last Updated: June 8, 2010
Health Authority: Canada: Health Canada

Keywords provided by Lawson Health Research Institute:
diabetes mellitus
islet transplantation

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

ClinicalTrials.gov processed this record on September 18, 2014