Anti-Thymocyte Globulin, Cyclosporine, and RAD in Islet Transplantation
NITA
A One-Year, Single-Center, Prospective, Open-Label Study of the Safety, Tolerability, and Preliminary Efficacy of Anti-Thymocyte Globulin, Cyclosporine, and RAD in Type 1 Diabetic Islet Transplant Recipients
1 other identifier
interventional
6
1 country
1
Brief Summary
This study was designed to test the safety and efficacy of up to 3 pancreatic alloislet transplants in type 1 diabetic patients with hypoglycemia unawareness. 6 subjects were transplanted under this protocol using anti-thymocyte globulin induction immunosuppression and everolimus with cyclosporine maintenance immunosuppression.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Mar 2003
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 1, 2003
CompletedFirst Submitted
Initial submission to the registry
February 2, 2006
CompletedFirst Posted
Study publicly available on registry
February 3, 2006
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2006
CompletedStudy Completion
Last participant's last visit for all outcomes
August 1, 2006
CompletedMay 8, 2008
May 1, 2008
3.4 years
February 2, 2006
May 2, 2008
Conditions
Outcome Measures
Primary Outcomes (3)
• The incidence, timing, and severity of adverse events during one year after the first and any subsequent islet transplants.
1 year
• Incidence and severity of hypoglycemia during the first year after the first and any subsequent islet transplants.
1 yr
• The proportion of recipients who develop alloantibodies directed at islet donor alloantigens during the first year after the first and any subsequent islet transplants.
1 year
Secondary Outcomes (5)
• The proportion of subjects who achieve insulin independence in the first year after single-donor or sequential transplantation.
1 year
• The proportion of islet allograft recipients with full and partial islet graft function at one year after the most recent islet transplant.
1 year
• Glycemic control and insulin secretory responses during the first year after the first and any subsequent transplants.
1 year
• The effect of donor age, pretransplant islet insulin secretory response in vitro, number of transplanted islet equivalents (IEQ), number of transplanted beta cells, pretransplant recipient insulin requirements and action, recipient body mass index (BM
Day of transplant
• The impact of islet transplantation on the quality of life of transplant recipients.
1 year
Study Arms (1)
1
EXPERIMENTALAllogeneic islet transplantation with anti-thymocyte globulin induction and cyclosporine and RAD maintenance immunosuppression
Interventions
Up to 3 intraportal infusions of cadaveric pancreatic islets of Langerhans. First infusion to contain at least 5,000 islet equivalents/kg body weight. Subsequent infusions to contain at least 3,000 islet equivalents/kg body weight.
Loading dose of 3 mg PO on day -2 relative to transplant, followed at least 12 hours later by dose of 1.5 mg PO BID. The daily dose will be adjusted according to the whole blood 12-hr trough to target 3-15 ng/ml for the first 3 months and 3-12 ng/ml thereafter.
A total of 6 mg/kg IV over 12 hours on days -2, -1, 0, +1, and +2. The dose will be 0.5 mg/kg on day -2, 1.0 mg/kg on day -1, and 1.5 mg/kg on days 0, +1, and +2.
Cyclosporine started on day +1 relative to the first islet transplant. Initial dose of 3 mg/kg/day administered in 2 divided doses; then adjusted to maintain target levels of 400 (350-500) ng/mL for the first three months following islet transplant and 300 (200-350) ng/mL thereafter.
Eligibility Criteria
You may qualify if:
- Primary islet allotransplant
- Patients with type 1 diabetes mellitus under intensive insulin management
- Age 18 or older
- Ability to give written informed consent
You may not qualify if:
- Age less than 18 years.
- BMI \>26 kg/m2.
- Insulin requirement of \> 50 IU per day.
- Positive C-peptide response to intravenous arginine stimulation.
- Untreated proliferative retinopathy.
- Creatinine clearance \< 60 ml/min/1.73 m2 for females and 70 ml/min/1.73 m2 for males.
- Serum creatinine \>1.3 mg/dl for females, \>1.5 mg/dl for males.
- Previous pancreas or islet transplant.
- Presence of history of panel-reactive anti-HLA antibodies \>10%.
- Positive pregnancy test, or presently breast-feeding, or failure to follow effective contraceptive measures.
- Active infection including hepatitis C, hepatitis B, HIV, or TB (or under treatment for suspected TB).
- Negative screen for Epstein-Barr Virus (EBV).
- Invasive aspergillus infection within year prior to study entry.
- History of malignancy.
- Active alcohol or substance abuse
- +15 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Minnesotalead
- Juvenile Diabetes Research Foundationcollaborator
- National Institutes of Health (NIH)collaborator
- Novartiscollaborator
Study Sites (1)
University of Minnesota
Minneapolis, Minnesota, 55455, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Bernhard J. Hering, M.D.
University of Minnesota
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
Study Record Dates
First Submitted
February 2, 2006
First Posted
February 3, 2006
Study Start
March 1, 2003
Primary Completion
August 1, 2006
Study Completion
August 1, 2006
Last Updated
May 8, 2008
Record last verified: 2008-05