Islet Transplantation for Type 1 Diabetes

• Status: Completed
• Trial end date: 2010-08-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to test whether the islet cell transplantation procedures and results from a previous study in Edmonton, Canada, can be repeated. The study also is designed to learn more about diabetes control using islet cell transplantation.

This is a Phase I/II study (a study that examines effectiveness and looks for side effects). The transplanting of islet cells has been studied in Type 1 diabetic patients whose blood sugar levels will not stay normal, despite intensive insulin therapy. A recent study conducted in Edmonton, Canada, was able to demonstrate that islet transplantation led to insulin independence in a majority of the patients treated. This study extends the results obtained from the Edmonton study, which used islet transplantation in Type 1 diabetic patients with steroid-free immunosuppression.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborator: Immune Tolerance Network (ITN)
• Treatments: Daclizumab; Ganciclovir; Ganciclovir triphosphate; Pentamidine; Sirolimus; Sulfamethoxazole; Tacrolimus; Trimethoprim

Criteria

Inclusion Criteria

Patients may be eligible for this study if they:

• Have had Type 1 diabetes mellitus for more than 5 years, and are exhibiting 1 of the following, despite intensive insulin management efforts: a) hypoglycemic unawareness, as defined by inability to sense hypoglycemia until the blood glucose falls to less than 54 mg/dL; b) metabolic instability, with 2 or more episodes of severe hypoglycemia (defined as an event with symptoms consistent with hypoglycemia in which the patient requires the assistance of another person and which is associated with a blood glucose below 54 mg/dL) or 2 or more hospital visits for diabetic ketoacidosis over the last year; or c) despite efforts at optimal glucose control, progressive secondary complications of diabetes as defined by retinopathy, nephropathy, or neuropathy.

• Are 18 to 65 years of age.

Exclusion Criteria

Patients will not be eligible for this study if they:

• Have had severe cardiac disease as defined by: a) recent myocardial infarction within the past 6 months; b) angiographic evidence of non-correctable coronary artery disease; or c) evidence of ischemia on a functional cardiac exam.

• Actively abuse alcohol or substances, including cigarette smoking (must not have smoked within the last 6 months).

• Have psychiatric problems that prevent them from being a suitable candidate for transplantation (such as schizophrenia, bipolar disorder, or major depression that is not controlled or stable on current medication).

• Have a history of not following prescribed regimens.

• Have active infection including hepatitis C virus, hepatitis B virus, human immunodeficiency virus (HIV), or Tuberculosis (TB) (or under treatment for suspected TB).

• Have a history of malignancy, except squamous or basal skin cancer.

• Weigh more than 70 kilograms or have a Body Mass Index (BMI) greater than 26 kg/m^2 at time of screening.

• Have a C-peptide value of 0.3 ng/ml or more following a 5.0 gram intravenous arginine infusion challenge.

• Are unable to provide informed consent.

• Have gallstones or hemangioma in liver.

• Have untreated proliferative retinopathy.

• Are breast-feeding or pregnant, or intend to try and become pregnant (females) or to father a child (males), or fail to follow birth control methods.

• Have had a previous transplant, or evidence of anti-human leukocyte antigen (HLA) antibody.

• Have an insulin requirement of more that 0.7 International Units (IU)/kilograms/day.

• Have a blood glycosylated hemoglobin (HbA1c) higher than 12 percent.

• Are unable to reach the hospital for transplantation within 2 hours of notification.

• Have untreated or treated hyperlipidemia.

• Have a medical condition requiring chronic use of steroids.

• Use coumadin or other anticoagulants (aspirin is allowed).

• Have Addison's disease.

• Have a negative screen for Epstein-Barr virus (EBV).