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
Intervention: Transplantation of Human Islets
Intervention description: Human islets, at least 9,000 islet equivalents per kilogram of body weight. Transplant involves surgical procedure
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Type 1 Diabetes; Islet Transplantation; Immunology

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Type 1 diabetes mellitus diagnosed > 5 years previously

          -  Body mass index less than or equal to 26

          -  18 to 65 years of age

          -  Compliance with an optimized diabetic management plan as assessed by an Emory
             University endocrinologist

          -  Checking and recording blood sugars at least 3 times per day

          -  Intensive insulin therapy (injecting insulin at least 3 times a day or using an
             insulin pump)

          -  Severe hypoglycemia and/or hyperglycemia. Severe hypoglycemia is defined by: episodes
             requiring assistance by others and/or hypoglycemic unawareness (the inability to
             recognize blood glucose < 54 mg/dL). Severe hyperglycemia is defined by: two episodes
             of ketoacidosis requiring hospitalization within the past year.

        Exclusion Criteria:

          -  Renal dysfunction

          -  Severe co-existing cardiac disease, characterized by any one of these conditions:
             recent myocardial infarction (within past six months); angiographic evidence of
             non-correctable coronary artery disease; or evidence of ischemia on a dobutamine
             stress echocardiogram.

          -  Current bacterial or fungal infection

          -  Macroproteinuria

          -  Baseline hemoglobin < 11.4 gm/dL in women; < 12.9 gm/dL in men.

          -  Hyperlipidemia

          -  Positive tests for human immunodeficiency virus (HIV), or hepatitis B or C

          -  Negative antibody test for varicella zoster virus (subjects may be reconsidered if
             they receive the vaccination and convert to a positive antibody)

          -  History of malignancy (except squamous or basal cell skin carcinoma)

          -  Previous/concurrent organ transplantation

          -  Presence of HLA panel reactive antibodies > 20%

          -  Active peptic ulcer disease

          -  Evidence of gallbladder disease including cholecystitis and cholelithiasis

          -  Evidence of liver disease including hepatic neoplasm, portal hypertension, or
             persistently abnormal liver function tests.

          -  Persistent coagulopathy or current use of anticoagulants (not including aspirin)

          -  Sickle cell anemia

          -  Positive pregnancy test, intent for future pregnancy, failure to follow effective
             contraceptive measures, or presently breastfeeding

          -  Active alcohol or substance abuse. This includes smoking (must be abstinent for six
             months). Active alcohol abuse should be considered using the current National
             Institute on Alcohol Abuse and Alcoholism (NIAAA) definitions.

          -  Psychiatric disorder making the subject not a suitable candidate for transplantation

          -  Current use of systemic steroid medications

          -  Evidence of insulin resistance (insulin requirement > 1.2 units/kg/day)

          -  Inability to provide informed consent

          -  Any condition or any circumstance that makes it unsafe to undergo an islet transplant