Raptiva and Sirolimus in Islet Transplantation for Type 1 Diabetes

• Status: Terminated
• Trial end date: 2012-08-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary objective of this protocol is to test the safety and efficacy of a treatment regimen consisting of maintenance therapy with efalizumab and sirolimus for 1 year followed by withdrawal of efalizumab and maintenance therapy with sirolimus, for the prevention of the destruction and rejection of islet transplants in type 1 diabetic recipients.

Genentech, the manufacturer of efalizumab voluntarily withdrew the drug from the U.S. market in April of 2009. Previously transplanted subjects have been transitioned to alternative immunosuppressives and no new subjects will be transplanted under this protocol.

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

Details

• Lead Sponsor: University of Minnesota; University of Minnesota - Clinical and Translational Science Institute
• Collaborator: Juvenile Diabetes Research Foundation
• Treatments: Antilymphocyte Serum; Everolimus; Sirolimus; Thymoglobulin

Criteria

Inclusion Criteria:

1. Primary islet allotransplant

2. Type I diabetes mellitus for a minimum of 5 years

3. One of the following signs or symptoms despite intensive efforts made in close cooperation with their diabetic care team:

• Metabolic lability/instability characterized by hypoglycemia or ketoacidosis (>2 hospital admissions in the previous year), erratic glucose profiles (MAGE>120 mg/dL), or disruption in lifestyle of 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 the diabetes care team)

• Progressive secondary complications as defined by (i) a new diagnosis by an ophthalmologist of proliferative retinopathy or clinically significant macular edema or therapy with photocoagulation during the last year; or (ii) urinary albumin excretion rate >300 mg/day but proteinuria <3g/day; or (iii) 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)

4. Age 18 to 65 years of age.

Exclusion Criteria:

1. Current use of immunosuppressive agents

2. Lymphopenia (<1000/µL) or leukopenia (<3000 total leukocytes/µL)

3. Presence of panel-reactive anti-HLA antibody >20%

4. Positive lymphocytotoxic cross-match using donor lymphocytes and serum

5. Evidence of acute EBV infection (IgM>IgG) OR negative screen for EBV by IgG determination

6. Calculated or measured GFR < 60 ml/min/m2

7. Portal hypertension or history of significant liver disease

8. History of malignancy within 10 years (except for adequately treated basal or squamous cell CA of the skin)

9. Active peptic ulcer disease

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

11. Untreated proliferative retinopathy

12. Pregnancy or breastfeeding

13. Female subjects not post-menopausal or surgically sterile, or not using an acceptable method of contraception

14. Active infections

15. Serologic evidence of infection with HIV, or HbsAg or HCV Ab positive

16. Major ongoing psychiatric illness

17. Ongoing substance abuse, drug or alcohol; or recent history of noncompliance

18. Any condition that in the opinion of the Principle Investigator would not allow for safe participation in the study