University of Massachusetts Medical School

Trials of Islet Cell Transplantation:
"Calcineurin-Inhibitor-Free Immunosuppression"

Introduction

Islet transplantation is a way of treating diabetes by giving a person new insulin-secreting islets. The “Edmonton Protocol” received widespread media attention in 2000 when researchers from the University of Alberta reported that they had developed a new method for transplanting islets that was successful in seven patients with Type 1 diabetes [New England Journal of Medicine, 343:230-8, 2000] . Many more patients have now been transplanted with this procedure, including two at UMass. Many but not all of those who received these transplants are now off insulin. Work is proceeding in many centers to develop even better protocols. One such protocol is called "Calcineurin-Inhibitor Free Immunosuppression," and we are now starting a study of this protocol at UMass in the near future.

Background

Pancreatic islets contain insulin-producing beta cells that regulate how the body utilizes glucose (or sugar). In Type 1 (or "Juvenile") diabetes, the immune system mistakenly attacks these cells, leaving people unable to make insulin. Islet transplantation restores the body's ability to produce insulin by implanting new functioning islet cells. These islets are usually obtained from cadaver donors.

Goals

Our goal is to learn if "Calcineurin-Inhibitor-Free Immunosuppression" will be superior to the Edmonton Protocol and reliably and safely reverse type 1 diabetes. To do so, we have applied for funding from the National Institutes of Health (NIH). We are also an affiliate of the Immune Tolerance Network (ITN) , which is a large NIH funded research group that has the same goal.

Criteria for enrollment

This study started in August, 2004. These are the enrollment criteria:

Only people between the ages of 18-65 years who have had Type 1 diabetes for at least 5 years are eligible. Candidates must have been in close contact with a physician during the 6 months preceding enrollment, during which intensive management of diabetes was attempted. Intensive management is defined as the administration of at least 3 insulin injections per day and self-monitoring of blood glucose at least 4 times per day.

In addition, despite conscientious adherence to dietary and lifestyle modifications, and an optimal insulin regime, at least one of the following applies:

• Evidence of poor control of diabetes, defined as a glycohemoglobin >8.0% on at least two occasions prior to enrollment.
• A history of recurring hypoglycemia and documented evidence of at least 3 episodes of hypoglycemia severe enough to be incapacitating.

Conditions that will disqualify persons from enrolling for as long as the condition is present

• Being overweight (body mass index >26)
• Being pregnant
• Significant kidney disease (creatinine clearance rate <60 ml/min)
• Liver disease (ALT or AST greater than twice normal, or portal hypertension)
• Current or prior infection with hepatitis B virus, hepatitis C virus, or HIV
• Bleeding problems (elevated PT or PTT)
• Cancer, abnormally elevated prostate-specific antigen (men), or an abnormal mammogram or pap test (women)

Persons with diabetes who would like to participate in this experimental research and who believe that they qualify for enrollment should know that enrollment in the trial is very limited. Meeting all of the basic entry criteria does not guarantee that you will be selected for an islet transplant. That being said, if you are interested in participating, please print out the application by clicking where it says "Download Application" below. After reading the application, if you think you are eligible and want to proceed, fill out your portion of the application. Then bring it and the rest of the paperwork to your physician. Because the entry criteria require technical medical information, a referral form must also be completed and signed by your physician.

Download Application (PDF)