Anti-Thymocyte Globulin, Cyclosporine, and RAD in Islet Transplantation

• Status: Completed
• Trial end date: 2006-08-01
• Target enrollment: 0
• Participant gender: All

Summary

This study was designed to test the safety and efficacy of up to 3 pancreatic alloislet transplants in type 1 diabetic patients with hypoglycemia unawareness. 6 subjects were transplanted under this protocol using anti-thymocyte globulin induction immunosuppression and everolimus with cyclosporine maintenance immunosuppression.

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

Details

• Lead Sponsor: University of Minnesota; University of Minnesota - Clinical and Translational Science Institute
• Collaborators: Juvenile Diabetes Research Foundation; National Institutes of Health (NIH); Novartis
• Treatments: Antilymphocyte Serum; Cyclosporine; Cyclosporins; Everolimus

Criteria

Inclusion Criteria:

• Primary islet allotransplant

• Patients with type 1 diabetes mellitus under intensive insulin management

• Age 18 or older

• Ability to give written informed consent

Exclusion Criteria:

• Age less than 18 years.

• BMI >26 kg/m2.

• Insulin requirement of > 50 IU per day.

• Positive C-peptide response to intravenous arginine stimulation.

• Untreated proliferative retinopathy.

• Creatinine clearance < 60 ml/min/1.73 m2 for females and 70 ml/min/1.73 m2 for males.

• Serum creatinine >1.3 mg/dl for females, >1.5 mg/dl for males.

• Previous pancreas or islet transplant.

• Presence of history of panel-reactive anti-HLA antibodies >10%.

• Positive pregnancy test, or presently breast-feeding, or failure to follow effective contraceptive measures.

• Active infection including hepatitis C, hepatitis B, HIV, or TB (or under treatment for suspected TB).

• Negative screen for Epstein-Barr Virus (EBV).

• Invasive aspergillus infection within year prior to study entry.

• History of malignancy.

• Active alcohol or substance abuse

• History of non-adherence to prescribed regimens.

• Psychiatric disorder making the subject not a suitable candidate for transplantation.

• Inability to provide informed consent.

• Baseline Hgb < 11.7 g/dl in females, or < 13 g/dl in males; lymphopenia (<1,000/microL), or leukopenia (<3,000 total leukocytes/microL), or an absolute CD4+ count <500/microL., or platelets <150,000/microL

• History of coagulopathy or medical condition requiring long-term anticoagulant therapy after transplantation or patient with INR >1.5.

• Severe co-existing cardiac disease.

• Baseline liver function tests outside of normal range or history of significant liver disease.

• Active peptic ulcer disease.

• Severe unremitting diarrhea or other gastrointestinal disorders potentially interfering with the ability to absorb oral medications.

• Presence of severe allergy requiring acute or chronic treatment, or hypersensitivity to drugs similar to RAD (e.g., macrolides).

• Known hypersensitivity to rabbit proteins.

• Hyperlipidemia (fasting LDL cholesterol > 130 mg/dl, treated or untreated; and/or fasting triglycerides > 200 mg/dl).

• Addison's disease.

• Under treatment requiring chronic use of systemic steroids.

• Any medical condition that, in the opinion of the investigator, will interfere with the safe completion of the trial.