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

• Status: Completed
• Trial end date: 2016-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of California, San Francisco
• Collaborator: Juvenile Diabetes Research Foundation
• Treatments: Abatacept; Immunosuppressive Agents

Criteria

Inclusion Criteria:

• 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)

Exclusion Criteria:

• 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