Southern California Islet Consortium
 
 
   
ISLET TRANSPLANTATION ALONE IN PATIENTS WITH DIFFICULT TO CONTROL TYPE 1 DIABETES MELLITUS
 


DESCRIPTION OF STUDY

Type 1 diabetes is associated with the damage of a specific cell subtype of pancreatic islets (clusters of cells in the pancreas that produce insulin and other metabolic hormones), which makes patients depend on an outside source of insulin. Despite insulin treatment, there is a significant risk of long-term problems, including damage to the heart, blood vessels, nerves, eyes and kidneys. The results of recent research studies suggest that these complications are caused by poor glucose control.

Transplantation of islets into the portal vein of the liver (the vein that carries blood from the gut and the pancreas to the liver) offers the prospect of good blood glucose control without the major surgical risks associated with whole pancreas transplant and may result in independence from insulin injections. Recently, a group of investigators in Edmonton, Canada used this method with a new regimen of anti-rejection drugs (to help prevent the rejection of transplanted islets) and showed that the regimen was effective in more than 75% of the cases who were followed up to 2 years.

This study is being performed to evaluate the safety and effectiveness of islet cell transplantation alone (ITA) in patients who have difficult to control type 1 diabetes mellitus without kidney failure. Difficult to control type 1 diabetes is defined as wide swings in blood glucose that disrupt the patient's life and result in frequent episodes of low blood glucose despite the proper use of standard insulin therapy and frequent blood glucose monitoring.

Patients between the ages of 18 and 60 with difficult to control type 1 diabetes mellitus without kidney failure may be eligible for this study if they meet the patient selection criteria. Candidates will be screened with a medical history, physical examination, blood tests, urinanalysis, electrocardiogram (EKG) and exercise test, chest x-ray, kidney ultrasound, and gall bladder ultrasound. These tests will help rule out the presence of diseases of the heart, liver, gallbladder and kidney and other chronic or debilitating diseases. A colonoscopy, mammography, and/or pap smear may also be necessary to rule out the presence of cancer. Other exams will be performed to evaluate insulin sensitivity and digestion rate prior to islet transplantation. Once a patient is found to qualify for the study, they will be placed on a waiting list for a donor pancreas. Some or all of these qualifying tests may need to be repeated if a patient remains on the waiting list for more than 3 months.

Before islet transplantation, patients will be prepped with anti-rejection drugs to suppress the immune system and prevent islet cell rejection. Antibiotics, vitamins (Vitamin C, Vitamin E, and nicotinamide), pravastatin, and iron will also be given just prior to transplantation to prevent infection, protect the newly implanted islets, and prevent post- transplant anemia.

Islets will be infused through a thin tube into the portal vein. After transplantation, two additional drugs will be administered, including inhaled pentamidine and an oral antiviral agent to prevent infection. Patients will remain in the hospital overnight to monitor for the development of complications, such as bleeding. During the post-transplant hospital stay, an ultrasound of the portal vein will be performed and blood will be drawn for routine tests every 8 hours. Blood sugar levels will be monitored frequently (before and after meals and at bedtime) and insulin doses will be adjusted accordingly.

Islet transplantation follow-up will involve frequent blood tests and clinic visits to monitor the blood levels of the anti-rejection drugs, evaluate for the development of complications and review blood glucose levels and insulin requirements. A variety of specialized tests will be performed to track improvements in blood sugar control and other health parameters, and to evaluate the immune system's response to transplanted islets. Follow-up for this study is expected to last for 2 years, but islet transplant recipients will require medical follow-up for the rest of their lives. Information collected on the islet transplantation procedure and its effectiveness in treating diabetes will be made available to all SC-IC participating centers and to the national agencies concerned including the Administrative and Bioinformatics Coordinating Center (ABCC) and the Collaborative Islet Transplantation Registry (CITR).

It is possible that two or even three islet transplantations may be required to provide enough islets to adequately cover a patient's insulin needs. If repeat transplantation is needed, the initial screening tests may need to be repeated. No more than three transplantations will be done on any given patient.