Islet Transplantation in Type 1 Diabetes (CIT-07)

You may be enrolled into this study, if you:

• are 18 to 65 years of age;
• have been diagnosed with type 1 diabetes with symptoms prior to age 40;
• are insulin dependent for at least 5 years, with three or more injections each day or on insulin pump therapy;
• have blood tests that show your body does not make insulin;
• are managing your diabetes daily, by checking you blood sugar at least three times a day;
• have had at least one episode of severe hypoglycemia in the past year where you needed the help of another person; and
• have hypoglycemia unawareness, a condition in which you no longer experience the usual warning signs of hypoglycemia.

The main purpose of this study is to determine the safety and effectiveness of islet transplantation, combined with immunosuppressive medications, for treating type 1 diabetes in individuals experiencing hypoglycemia unawareness and severe hypoglycemic episodes.

The goal of this study is to find out if islet transplantation successfully controls blood glucose levels in individuals with type 1 diabetes without the need for insulin injections. The effectiveness of islet transplantation will be measured by the proportion of people with an HbA1c < 6.5% and free of severe hypoglycemic events at 1 year after the first islet transplant.

If you enroll, you will be randomly (by chance) assigned to this study, or another islet transplantation study at the site, which uses an investigational medication as part of the immunosuppressive regimen. The group you are assigned to is decided by chance (as by the toss of a coin). Neither you nor your doctor will be able to choose which group you are in.

If you are assigned to this study, you will receive up to three separate islet transplants and a regimen of immunosuppressive medications consisting of anti-thymocyteglobulin (ATG), etanercept, sirolimus, and low-dose tacrolimus. You will begin receiving ATG and sirolimus 2 days prior to the first islet transplant. ATG will continue to be given until Day 2 post-transplant, and sirolimus will be given for the duration of the study. On Day 1 post-transplant, participants will receive tacrolimus, which will also be taken for the duration of the study. Etanercept will be taken on the day of transplant and Days 3, 7, and 10 post-transplant.

Transplantations will involve an inpatient hospital stay and infusion of islets into a branch of the portal vein. Participants who do not achieve or maintain insulin independence by Day 75 post-transplant will be considered for a second islet transplant. Participants who remain dependent on insulin for longer than 1 month after the second transplant and who show partial graft function will be considered for a third islet transplant. Daclizumab will be used in place of ATG for the second and third transplants, if they are necessary. Participants who do not meet the criteria for a subsequent transplant and do not have a functioning graft will enter a reduced follow-up period.

There will be up to 15 study visits following each transplant. A physical exam, review of adverse events, and blood collection will occur at most visits. A chest x-ray, abdominal ultrasound, electrocardiogram, quality of life questionnaires, urine collection, and glomerular filtrating rate (GFR) testing will occur at some visits. Participants will also test their own blood glucose levels at least five times per day throughout the study. A 12-month follow-up period will take place after the participant’s last transplant.

You cannot participate in any other research studies in which treatments are given. However, it may be possible for you to participate in other kinds of studies that do not involve intervention.

See contact information below.