Prevention of Autoimmune Destruction and Rejection of Human Pancreatic Islets Following Transplantation for Insulin Dependent Diabetes Mellitus

Trial Summary

Pancreatic islets are the part of the pancreas that produce insulin and help control the blood sugar. This study aims to improve islet transplantation as a treatment for Type 1 Diabetes by using a new combination of immunosuppressive drugs that have been successful in treating other autoimmune diseases and in preventing kidney transplant rejection.

Eligibility

• Type 1 Diabetes
• Metabolic lability/instability characterized by hypoglycemia or ketoacidosis(>2
  hospital admissions in the previous year), erratic glucose profiles(MAGE >120mg/dL),
  or disruption in lifestyle(danger to life, self or others). Reduced awareness of
  hypoglycemia or > 1 episode in the last 1.5 years of severe hypoglycemia.
• Persistently poor glucose control (as defined by HgbA1c>10% at the end of six months
  of intensive management efforts with diabetes care team.
• Progressive secondary complications as defined by
      - a new diagnosis by an ophthalmologist of proliferative retinopathy or clinically
         significant macular edema or therapy with photocoagulation during the last year;
         or
      - urinary albumin excretion rate >300mg/day but proteinuria <3g/day; or
      - symptomatic autonomic neuropathy (as defined by postural hypotension in the
         setting of euvolemia, gastroparesis or diarrhea attributed to diabetic
         neuropathy, or neuropathic bladder as diagnosed by an urologist)

• Patient weighs more than 80kg or body mass index BMI>28
• Patient's insulin requirement is >55 Units/day.
• Current use of immunosuppressive agents.
• History of malignancy within 10 years (except for adequately treated basal or
  squamous cell CA of the skin).
• Active peptic ulcer disease.
• Severe unremitting diarrhea or other GI disorders potentially interfering with the
  ability to absorb oral medications.
• Untreated proliferative retinopathy.
• Pregnancy or breastfeeding.
• Female subjects not post-menopausal or surgically sterile, or not using an acceptable
  method or contraception.
• Active infections.
• Major ongoing psychiatric illness.
• Ongoing substance abuse, drug or alcohol; or recent history of noncompliance.
• Portal hypertension or history of significant liver disease.
• Lymphopenia (<1000/ul) or leukopenia (<3000 total leukocytes/ul) or an absolute CD4
  count <500/ul.
• Presence or history of panel-reactive anti-HLA antibody >20%.
• Evidence of acute EBV infection (IgM>IgG) OR no serologic evidence of previous
  exposure to EBV (IgG>IgM).
• Serologic evidence of infection with HIV or HbsAg or HCV Ab positive.
• Creatinine clearance <60ml/min/m2.
• Positive lymphocytoxic cross-match using donor lymphocytes and serum

Detailed Description

Final eligibility is determined by the health professionals conducting the trial and the protocol approved by the Committee on Human Resources (CHR) at the University of California, San Francisco (UCSF). The Patient Consent Form for this trial is available upon request. For more information about this trial, please see the full posting at ClinicalTrials.gov.

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