Safety and Effectiveness of Low Molecular Weight Sulfated Dextran in Islet Transplantation After Kidney Transplant

This is an interventional treatment trial for Diabetes Mellitus, Type I focused on measuring Insulin dependence Read More

Inclusion Criteria:

• Subjects able to provide written informed consent and comply with study procedures
• Clinical history compatible with T1D and onset of disease at less than 40 years of age and insulin dependence for more than (>) 5 years at the time of enrollment; AND the sum of subject age and insulin-dependent diabetes duration is >=28
• Absent stimulated C-peptide (less than 0.3 ng/mL) 60 and 90 minutes post-mixed-meal tolerance test (MMTT)
• Subjects >6 months post renal (kidney) transplant, currently taking or willing to switch to appropriate maintenance immunosuppression
• Stable renal function and free of rejection for >=3 months prior to islet transplantation
• Standard medical treatment for >=3 months under the care of an experienced diabetologist and at the end of this period has had at least 1 severe hypoglycemic event OR a hemoglobin A1C (HbA1c) >7.2% OR reduced awareness of hypoglycemia manifest by a Clark score of >=4 in the last year prior to study entry

Exclusion Criteria:

• Known immunoglobulin E (IgE) mediated allergy to antibiotics used in islet culture medium
• Known hypersensitivity to dextran
• Measured glomerular filtration rate (GFR) using Iothalmate, 51Cr-EDTA, 99-technetium-DPTA, or iohexol of less than 40ml/min/1.73 m^2
• Proteinuria (albuminuria greater than 500 mg in 24 hours) of new onset since kidney transplantation
• Other (non-kidney) organ transplants except prior failed pancreatic graft
• Body mass index (BMI) >30 kg/m^2
• Insulin requirement of >1.0 IU/kg/day
• Consistently abnormal liver function tests (aspartate aminotransferase(AST), alanine aminotransferase (ALT),alkaline phosphatase, or total bilirubin) of greater than 1.5 times the upper limit of normal for two consecutive measurements that are >2 weeks apart
• Untreated proliferative diabetic retinopathy
• History of hypercoagulability disorder or coagulopathy or International Normalized Ratio(INR) that is >1.5
• Activated Protein C Resistance (APC-R)
• Evidence by serologies and PCR of acute or chronic active Epstein-Barr Virus (EBV) infection OR no evidence by EBV serologies of prior EBV exposure
• Any history of malignancy except for completely resected squamous or basal cell carcinoma of the skin

• Known history of severe co-existing cardiac disease, characterized by any one of the following conditions:

  1. Recent myocardial infarction (<=6 months)
  2. Evidence of ischemia on functional cardiac exam <=last year
  3. Left ventricular ejection fraction <30%
• Active infections, unless treatment is not judged necessary by the investigators(including but not limited to mild skin and nail fungal infections)
• Active infection including hepatitis B, hepatitis C,human immunodeficiency virus (HIV), or pulmonary tuberculosis
• Subjects with active peptic ulcer disease, symptomatic gallstones or portal hypertension
• Acute or chronic pancreatitis
• Subjects who are pregnant or breastfeeding, or who intend to become pregnant
• Sexually-active females who are not: a) post-menopausal, b) surgically sterile, or c) using an acceptable method of contraception: oral contraceptives, Norplant, Depo-Provera, and barrier devices combined with spermicidal gel are acceptable; condoms used alone are not acceptable.
• Active alcohol or substance abuse
• Evidence of high-level sensitization (Panel Reactive Antibodies (PRA) >50%) or positive cross match or the known presence of anti-donor HLA class I antibodies
• Treatment with any anti-diabetic medication, other than insulin, <=4 weeks of enrollment
• Use of any investigational agents <=4 weeks of enrollment
• Receipt of live attenuated vaccine(s) <=2 months of enrollment
• Subjects with any condition or circumstance that in the opinion of the investigator would make it unsafe to undergo an islet transplantation