Clinical Islet Transplantation Using the Edmonton Protocol

March 13, 2017 updated by: Lawson Health Research Institute
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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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.

Study Type

Observational

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • London, Ontario, Canada, N6A 4L6
        • London Health Sciences Centre University Campus

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Efficacy
Time Frame: 1 year
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Lawson Health Research Institute

Collaborators

London Health Sciences Centre

Investigators

  • Principal Investigator: William Wall, MD, Western University, Canada

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Completion

January 1, 2008

Study Registration Dates

First Submitted

March 29, 2006

First Submitted That Met QC Criteria

March 29, 2006

First Posted (Estimate)

March 31, 2006

Study Record Updates

Last Update Posted (Actual)

March 15, 2017

Last Update Submitted That Met QC Criteria

March 13, 2017

Last Verified

June 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • R-05-873
  • 11898

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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