Switch From Calcineurin Inhibitor to Belatacept in Pancreas Transplant Recipients

Study Overview
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Brief Summary
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Kidney damage is a major complication of current antirejection medicines used in transplantation. An increasing number of brittle diabetics are successfully receiving a pancreas transplant. One of the challenges following pancreas transplant is that a patient can develop kidney damage from one of their antirejection medicines, tacrolimus. The objective of this study is to substitute a new antirejection medicine which does not cause kidney damage, belatacept for tacrolimus in patients that have developed signs of tacrolimus related kidney damage to slow the progression of kidney disease.

Detailed Description
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Nephrotoxicity is a major complication of current immunosuppression regimens used in transplantation. Pancreas transplantation has been increasedly performed to manage labile diabetes mellitus during the last few decades and survival rates of pancreatic grafts are improving. One of the challenges that is faced following pancreas transplantation alone are pathologic changes from diabetes frequently seen in native kidneys in the pancreas transplant recipients. High levels of calcineurin inhibitors (CNI) have been identified as risk factors for decline in kidney function and progression to end-stage renal disease. The objective of this trial is to take subjects who have biopsy proven CNI toxicity off of their CNI and begin belatacept, which is not a CNI. The hypothesis is by switching the pancreas transplant subject with documented CNI kidney toxicity to belatacept will slow the progression of chronic kidney disease.

Official Title
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Calcineurin Inhibitors to Belatacept Switch Study to Prevent the Progression of Kidney Disease in Pancreas Transplant Alone Recipients

Conditions
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Nephrotoxicity

Intervention / Treatment
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* Drug: Belatacept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pancreas transplant alone recipients EBV IgG positive Biopsy proven calcineurin inhibitor toxicity on native kidney biopsy Maintained on a regimen of tacrolimus, sirolimus, mycophenolate Exclusion Criteria: EBV IgG negative Not maintained on an immunosuppression regimen that contains tacrolimus Unable or unwilling to give informed consent Active infection History of malignancy post transplant Glomerular filtration rate < 15 mL/min

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: belatacept<br>Belatacept 5 mg/kg IVPB q 2 wks x 5 doses followed by 5 mg/kg IVPB q month. The belatacept dose will be infused IV over 30 minutes. Day 14: Reduce tacrolimus dose by 25% Day 30: Reduce tacrolimus dose by additional 25% Day 45: Reduce tacrolimus dose by additional 25% Day 60: Stop tacrolimus. | Drug: Belatacept<br> <br> * Other names: Nulojix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Serum Estimated Glomerular Filtration Rate (eGFR) | Change in serum eGFR from baseline to 1 year following conversion from tacrolimus to belatacept | Baseline and 1 year | 
| Serum Creatinine at Year 1 | Serum Creatinine measured at 1 year after conversion from Tacrolimus to Belatacept. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Pancreas Transplant Rejection | Pancreas Rejection as measured by serum amylase, serum lipase. | 1 year | 
| Change From Baseline Serum Hemoglobin A1c | Pancreas Transplant Function was measured by assessing change in Pre HbA1c to Post HbA1c at1 year after conversion. | Baseline and 1 year | 
| Pancreas Transplant Function as Measured by Fasting Serum Glucose Level. | Fasting Serum Glucose level measured at 1 year after conversion from Tacrolimus to Belatacept. | 1 Year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pancreas transplantation, immunosuppression, belatacept