B-Lymphocyte Immunotherapy in Islet Transplantation for Initial Islet Graft Failure

No longer available
Trial end date:
Target enrollment:
Participant gender:
Type 1 diabetes is an autoimmune disease in which the insulin-producing pancreatic beta cells are destroyed, resulting in poor blood sugar control. The purpose of this study is to determine the safety and effectiveness of islet transplantation, combined with immunosuppressive medications and medications to support islet survival for treating type 1 diabetes in individuals experiencing hypoglycemia unawareness and severe hypoglycemic episodes.
Accepts Healthy Volunteers?
Lead Sponsor:
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Anti-Bacterial Agents
Antifungal Agents
Antiviral Agents
Calcineurin Inhibitors
Inclusion Criteria:

- Enrolled in clinical trial DAIT CIT-05 (NCT00468442)

- Islet graft failure: absent stimulated C-peptide (<0.3ng/mL) in response to mixed meal
tolerance test

Exclusion Criteria:

- Untreated proliferative diabetic retinopathy

- Blood Pressure: systolic blood pressure>160mmHg or diastolic blood pressure>100mmHg

- Measured glomerular filtration rate (GFR) using iohexol < 80ml/min/1.73m^2 Strict
vegetarians with a calculated GFR < 70ml/min/1.73m^2

- Presence or history of macroalbuminuria > 300mg/g of creatinine

- Presence or history of panel-reactive anti-HLA antibodies above background by flow

- For female participants: Positive Pregnancy Test, presently breast-feeding, or
unwillingness to use effective contraceptive measures for the duration of the study
and 3 months after discontinuation. For male participants: intent to procreate during
the duration of the study or within 3 months after discontinuation or unwillingness to
use effective measures of contraception. Oral contraceptives, Norplant, Depo-Provera
and barrier devices with spermicide are acceptable contraceptive methods; condoms used
alone are not acceptable.

- Active infection including hepatitis B, hepatitis C, HIV, or TB as determined by a
positive skin test or clinical presentation, or under treatment for suspected TB.
Positive tests are acceptable only if associated with a history of previous
vaccination in the absence of any sign of active infection. Positive tests are
otherwise not acceptable, even in the absence of any active infection at the time of

- Negative screen for Epstein-Barr Virus (EBV) by IgG determination

- Invasive aspergillus, histoplasmosis, or coccidiomycosis infection within one year
prior to study enrollment

- Any history of malignancy except for completely resected squamous or basal cell
carcinoma of the skin

- Known active alcohol or substance abuse

- Anemia (Hgb < 11 g/dL),neutropenia (<1,500/µL), or thrombocytopenia (platelets

- A history of Factor V deficiency

- Any coagulopathy or medical condition requiring long-term anticoagulant therapy (e.g.,
warfarin) after transplantation (low-dose aspirin treatment is allowed) or patients
with an International Normalized Ratio (INR) >1.5

- Severe co-existing cardiac disease, characterized by any one of these conditions:

1. recent myocardial infarction (within past 6 months)

2. evidence of ischemia on functional cardiac exam within the last year

3. left ventricular ejection fraction <30%

- Persistent elevation of liver function tests (LFTs) at the time of study entry (e.g.,
persistent SGOT (AST), SGPT (ALT), Alk Phos or total bilirubin, with values >1.5 times
normal upper limits

- Symptomatic cholecystolithiasis

- Acute or chronic pancreatitis

- Symptomatic peptic ulcer disease

- Severe unremitting diarrhea, vomiting or other gastrointestinal disorders potentially
interfering with the ability to absorb oral medications

- Hyperlipidemia despite medical therapy (fasting LDL cholesterol > 130 mg/dL, treated
or untreated; and/or fasting triglycerides > 200 mg/dL)

- Receiving treatment for a medical condition requiring chronic use of systemic
steroids, except for the use of ≤ 5 mg prednisone daily, or an equivalent dose of
hydrocortisone, for physiological replacement only

- Use of any investigational agents within 4 weeks of enrollment

- Administration of live attenuated vaccine(s) within 2 months of enrollment

- Any medical condition that, in the opinion of the investigator, will interfere with
the safe completion of the trial, such as chronic central neurologic disease

- Treatment with any anti-diabetic medication other than insulin within 4 weeks of

- A previous pancreas transplant, unless the graft failed within the first week due to
thrombosis, followed by pancreatectomy and the transplant occurred more that 6 months
prior to enrollment