Status:
COMPLETED
hOKT3γ1 (Ala-Ala) Combined With Sirolimus and Delayed Tacrolimus in Type 1 Diabetic Islet Allograft Recipients
Lead Sponsor:
University of Minnesota
Collaborating Sponsors:
Juvenile Diabetes Research Foundation
Conditions:
Type 1 Diabetes
Hypoglycemia
Eligibility:
All Genders
18-65 years
Phase:
PHASE1
PHASE2
Brief Summary
The collective effects of two-layer pancreas preservation, pretransplant islet culture, day -2 pretransplant immunosuppression, and induction immunosuppression with the FcR-nonbinding anti-CD3 monoclo...
Detailed Description
This is an open-label, one-year follow-up study of type 1 diabetic islet allograft recipients who receive FcR non-binding OKT3 antibody hOKT3γ1 (Ala-Ala) plus sirolimus induction immunotherapy combine...
Eligibility Criteria
Inclusion
- Primary islet allotransplant
- Type 1 diabetes mellitus, complicated by at least one of the following situations that persist despite intensive efforts in close cooperation with their diabetes care team:
- Metabolic lability/instability;
- Reduced awareness of 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.
- Age 18 and older
- Able to give written informed consent
Exclusion
- Age less than 18 years
- Body weight greater than75 kg.
- BMI greater than 26 kg/m2 for male and females
- Waist-to-hip ratio 0.80 (female) and 0.95 (male)
- First degree relative with type 2 diabetes
- Insulin requirement of greater than 0.7 IU/kg/day
- HbA1C greater than 12%
- Positive C-peptide response to intravenous arginine stimulation
- Untreated proliferative retinopathy
- Macroalbuminuria (urinary albumin excretion greater than 300 mg/24hrs)
- Creatinine clearance greater than 85 ml/min/1.73 m2 in females, greater than 95 ml/min/1.73 m2 in males
- Serum creatinine greater than 1.2 mg/dl
- Previous pancreas or islet transplant
- Previous OKT3 antibody therapy
- Presence of history of panel-reactive anti-HLA antibodies greater than 10%
- Abnormal T4 and TSH despite thyroid replacement therapy
- Positive pregnancy test, or presently breast-feeding
- Active infection
- Negative screen for Epstein-Barr Virus (EBV) by an EBNA method
- Invasive aspergillus infection within year prior to study entry
- Any 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
- Karnofsky performance score greater than 70
- Baseline Hgb greater than 11.7 g/dl; lymphopenia (greater than 1,000/L), or leukopenia (greater than 4,000 total leukocytes/L), or an absolute CD4+ count \<500/L
- Thrombocytopenia greater than 150 x 109/L
- Use of warfarin or other anticoagulant therapy (except aspirin) or patient with PT-INR greater than 1.5
- Severe co-existing cardiac disease
- Baseline liver function tests outside of normal range
- Presence of gallstones on baseline ultrasound exam
- Active peptic ulcer disease
- Severe unremitting diarrhea or other gastrointestinal disorders potentially interfering with the ability to absorb oral medications
- Celiac disease
- Hyperlipidemia (fasting LDL cholesterol greater than 130 mg/dl, treated or untreated; and/or fasting triglycerides greater than 200 mg/dl)
- Addison's disease.
- Under treatment for a medical condition 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
Key Trial Info
Start Date :
April 1 2000
Trial Type :
INTERVENTIONAL
End Date :
January 1 2004
Estimated Enrollment :
6 Patients enrolled
Trial Details
Trial ID
NCT00285194
Start Date
April 1 2000
End Date
January 1 2004
Last Update
August 2 2012
Active Locations (1)
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1
Universtiy of Minnesota
Minneapolis, Minnesota, United States, 55455