Islet Transplantation in Type 1 Diabetics Using the Edmonton Protocol of Steroid Free Immunosuppression
Condition: Diabetes Mellitus, Type 1
MeSH terms: Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 2

Summary: 
      This trial will study the ability of islet transplantation to restore glycemic control and
      achieve insulin independence in type 1 diabetic subjects with life-threatening hypoglycemia
      and unawareness, or recurrent hyperglycemia with ketoacidosis.
    

Detailed description: 
      LAY SUMMARY:

      More than 1 million North Americans have type 1 diabetes. Each year, approximately 30,000 new
      cases of type 1 diabetes are diagnosed in the United States. Type 1 diabetes destroys islets,
      a cluster of cells within the pancreas that produce insulin. Insulin is a hormone with many
      effects. However, the most important effect of insulin is to control the level of sugar in
      the blood. People with Type 1 diabetes no longer produce insulin and must take insulin
      injections to live. Despite steady improvements in the management of this disease, its
      victims remain at increased risk for stroke, heart attack, kidney failure, amputation,
      blindness, nerve damage and premature death. The life expectancy of a teenager is reduced by
      thirty years from the time of onset of the disease. Unfortunately, many type 1 diabetics
      cannot control their blood sugars in spite of very careful monitoring and the frequent
      injection of insulin. This group of patients is considered to have labile or "brittle"
      diabetes. These "brittle" diabetics can often have wide swings in their blood sugar levels
      that can be life threatening. Hypoglycemia, or low blood sugars, occurs when too much insulin
      is in the bloodstream. When this occurs, it is vital that patients eat or drink something
      right away that will increase their blood sugars. Many diabetics lose the ability to
      recognize when their blood sugars are getting dangerously low. These episodes of hypoglycemia
      can lead to coma, and possibly death, if not recognized and treated right away. Patients can
      also experience extreme increases in blood sugars, or hyperglycemia, as a result of emotional
      or physical stress. Hyperglycemia can result in dehydration, confusion, and a condition
      called ketoacidosis, which can lead to death. When this happens, insulin must be given as
      soon as possible.

      Islet transplantation can restore the body's ability to make insulin and, in turn, restore
      normal blood sugar levels.

      Since the 1960's, doctors and scientists have attempted to replace this islet function by
      performing whole organ pancreas transplantation. While the results of pancreas
      transplantation have improved dramatically in recent years, this approach has largely been
      limited to patients with kidney disease who have also needed a kidney transplant. This is
      because of the risks associated with the surgical procedure and the immunosuppressive drugs
      required to prevent rejection or the destruction of the transplanted pancreas by the body's
      immune system. Transplantation of a whole pancreas requires a major operation that is done
      through an incision in the abdomen. The patient must be under general anesthesia, or asleep,
      for the entire procedure. Recent clinical experience suggests that islet transplantation may
      be a useful approach to correct diabetes in humans.

      Islet transplantation offers a direct approach to the treatment of type 1 diabetes. A large
      number of experimental studies carried out in many laboratories over the last decade have
      documented the beneficial effects of islet transplants in experimental animals. These
      experiments have confirmed both the efficiency and safety of islet transplantation.

      The inability to isolate enough islets from a single pancreas has been one obstacle to
      successful islet transplantation. A certain number of islets must be isolated, or separated,
      from a single pancreas in order to use them for transplant. If this minimum number of islets
      is not obtained, then the islets do not effectively reverse diabetes. Progress in isolating
      the islets from a human pancreas has been dramatic in the last several years. Advances in
      equipment and technology have lead to increases in the number of islets that can be isolated
      from a single pancreas.

      After successful isolation, the islets can be injected through a catheter into the patient's
      liver during a thirty-minute procedure. A group of doctors at the University of Alberta in
      Edmonton, Canada has had promising results in human islet transplantation. Normal sugar
      levels have been documented after human islet transplants. Also, recent improvements in
      immunosuppressive drug treatments have resulted in sustained insulin-independence in selected
      type 1 diabetic patients. The traditional method of transplant immunosuppression includes
      using some form of a steroid drug. Steroids have been found to injure or kill the islets
      after transplant. The doctors in Edmonton, Canada established an immunosuppression formula
      that does not use steroids. The objective of the study here at Emory University is to
      reproduce the successful results of human islet transplantation that have been achieved by
      the doctors at the University of Alberta using steroid free immunosuppression.

      The Emory Islet Transplant Program will enroll ten patients, ages 18 to 65, in the study.
      Each of the ten patients will receive at least 2 islet transplants from 2 different organ
      donors. A third transplant may be required based on the patient's insulin requirements after
      the 1st two transplants. Each patient will be placed on immunosuppressive drugs to prevent
      the body from rejecting or destroying the transplanted islets. Each patient will have his/her
      blood sugar levels and insulin requirements monitored very closely after each transplant. The
      patients will also have various tests to determine if their diabetic complications improve,
      remain the same, or become worse. The patients will be asked to record any episodes of
      hypoglycemia or low blood sugars while participating in this study. Emory will examine
      whether or not there is a decrease in how often the episodes occur. Patients will also
      undergo regular eye exams to document retinal changes or improvements that may occur after
      transplant. At this time it is not known whether islet transplantation slows or stops the
      progression of common diabetic complications. More experience and research is needed before
      this can be determined. One focus of our research will be to study diabetic complications in
      patients who receive islet transplants.

      The major goal of the Emory Islet Transplant Program is for patients participating in this
      study to be free of the need for insulin injections after 2 islet transplants. Because many
      advances have been made in islet transplantation, the transplant team at Emory would like to
      participate in this promising treatment of type 1 diabetes and, most importantly, help those
      who suffer from this disease become free from daily insulin injections and avoid the
      devastating complications that happen as a result of diabetes.
    

Intervention name(s): Transplantation of Human Islets
Intervention type(s): Drug
Intervention description(s): Human islets, at least 9,000 islet equivalents per kilogram of body weight. Transplant involves surgical procedure
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Type 1 Diabetes; Islet Transplantation; Immunology