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

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

Inclusion Criteria:

• Mentally stable and able to comply with study procedures;

• Clinical history compatible with type 1 diabetes, with:

  • onset of disease at less than 40 years of age,
  • insulin dependence for at least 5 years at study entry, and
  • sum of age and insulin-dependent diabetes duration of at least 28.
• Absent stimulated C-peptide (less than 0.3 ng/ml) 60 and 90 minutes post-mixed-meal tolerance test;

• Involvement of intensive diabetes management, defined as:

  • Self-monitoring of glucose values no less than a mean of three times each day, averaged over each week,
  • Administration of three or more insulin injections each day or insulin pump therapy,
  • Under the direction of an endocrinologist, diabetologist, or diabetes specialist, with at least three clinical evaluations during the past 12 months.
• At least one episode of severe hypoglycemia in the past 12 months, defined as an event with symptoms compatible with hypoglycemia in which the individual required assistance of another person and which was associated with either a blood glucose level less than 54 mg/dl or prompt recovery after an oral carbohydrate, intravenous glucose, or glucagon administration; and
• Reduced awareness of hypoglycemia OR marked glycemic lability OR a composite of a Clarke score of 3 or more or a HYPO score greater or equal to the 75th percentile in the 12 months prior to randomization.

Exclusion Criteria:

• Known IgE mediated allergy to antibiotics used in the culture medium;
• Known hypersensitivity to dextran;
• Body mass index (BMI) greater than 30 kg/m^2;
• Insulin requirement of more than 1.0 IU/kg/day;
• HbA1c greater than 10%;
• Untreated proliferative diabetic retinopathy;
• Systolic blood pressure higher than 160 mmHg or diastolic blood pressure higher than 100 mmHg;
• Measured glomerular filtration rate (GFR) using 51Cr-EDTA, 99technetium-DPTA, or iohexol of less than 80 ml/min/1.73m^2;
• Presence or history of macroalbuminuria (greater than 300 mg/g creatinine);
• Presence or history of panel-reactive anti-HLA antibody levels greater than 20% by flow cytometry;
• Pregnant, breastfeeding, or unwilling to use effective contraception throughout the study and for 4 months after study completion;
• Active infection, including hepatitis B virus, hepatitis C virus, HIV, or tuberculosis;
• Negative for Epstein-Barr virus by IgG determination;
• History of malignancy with exception of completely resected squamous or basal cell carcinoma of the skin;
• Known active alcohol or substance abuse;
• Baseline Hgb below the lower limits of normal, lymphopenia, neutropenia, or thrombocytopenia;
• Activated protein C resistance (APC-R);
• Any coagulopathy or individuals with an INR greater than 1.5;

• Severe coexisting cardiac disease, characterized by any one of the following conditions:

  • Heart attack within the last 6 months,
  • Evidence of ischemia on functional heart exam within the year prior to study entry, or
  • Left ventricular ejection fraction less than 30%.
• Persistent elevation of liver function tests at the time of study entry;
• Acute or chronic pancreatitis;
• Active peptic ulcer disease, symptomatic gallstones, or a history of portal hypertension;
• Severe unremitting diarrhea, vomiting, or other gastrointestinal disorders that could interfere with the ability to absorb oral medications;
• Currently receiving treatment for a medical condition that requires chronic use of systemic steroids;
• Treatment with any antidiabetic medication other than insulin, within 4 weeks prior to study entry;
• Use of any investigational medications within the past 4 weeks;
• Received a live attenuated vaccine within the past 2 months;
• Treatment with any immunosuppressive regimen at time of study entry;
• Previous islet transplant;

• Previous pancreas transplant.

  --Note: Participants who had a pancreas transplant more than 6 months prior to study entry that failed within the first week due to thrombosis, followed by surgical removal of the transplanted pancreas, are not excluded.

• Or any medical condition that, in the opinion of the investigator, might interfere with safe participation.