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

June 9, 2014 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

B-Lymphocyte Immunotherapy in Islet Transplantation: Single Subject Modification to Calcineurin-Inhibitor Based Immunosuppression for Initial Islet Graft (CIT-0501)

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.

Study Overview

Status

No longer available

Conditions

Intervention / Treatment

Detailed Description

Type 1 diabetes is commonly treated with the administration of insulin, either by multiple insulin injections or by a continuous supply of insulin through a wearable pump. Insulin therapy allows long-term survival in individuals with type 1 diabetes; however, it does not guarantee constant normal blood sugar control. Because of this, long-term type 1 diabetic survivors often develop vascular complications, such as diabetic retinopathy, an eye disease that can cause poor vision and blindness, and diabetic nephropathy, a kidney disease that can lead to kidney failure. Some individuals with type 1 diabetes develop hypoglycemia unawareness, a life-threatening condition that is not easily treatable with medication and is characterized by reduced or absent warning signals for hypoglycemia. For such individuals, pancreas or pancreatic islet transplantation are possible treatment options. Insulin independence among islet transplant recipients tends to decline over time. New strategies aimed at promoting engraftment of transplanted islets are needed to improve the clinical outcomes associated with this procedure.

Study Type

Expanded Access

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Hospital of the University of Pennsylvania

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 cytometry
  • 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 evaluation.
  • 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 <100,000/µL)
  • 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 enrollment
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

First Submitted

January 12, 2010

First Submitted That Met QC Criteria

January 12, 2010

First Posted (Estimate)

January 14, 2010

Study Record Updates

Last Update Posted (Estimate)

June 11, 2014

Last Update Submitted That Met QC Criteria

June 9, 2014

Last Verified

June 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DAIT CIT-0501

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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