Nephrotoxicity
Conditions
Keywords
pancreas transplantation, immunosuppression, belatacept
Brief summary
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
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.
Interventions
DRUGBelatacept
Sponsors
Indiana University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Serum Estimated Glomerular Filtration Rate (eGFR) | Baseline and 1 year | Change in serum eGFR from baseline to 1 year following conversion from tacrolimus to belatacept |
| Serum Creatinine at Year 1 | 1 year | Serum Creatinine measured at 1 year after conversion from Tacrolimus to Belatacept. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Pancreas Transplant Rejection | 1 year | Pancreas Rejection as measured by serum amylase, serum lipase. |
| Change From Baseline Serum Hemoglobin A1c | Baseline and 1 year | Pancreas Transplant Function was measured by assessing change in Pre HbA1c to Post HbA1c at1 year after conversion. |
| Pancreas Transplant Function as Measured by Fasting Serum Glucose Level. | 1 Year | Fasting Serum Glucose level measured at 1 year after conversion from Tacrolimus to Belatacept. |
Countries
United States
Participant flow
Recruitment details
First patient enrolled and started on June 3, 2014. Last patient enrolled and started on Aug 6, 2014. All patients enrolled at Indiana University Hospital - Transplant Unit.
Pre-assignment details
Participants were enrolled according to inclusion and exclusion criteria. Tacrolimus was weaned according to protocol.
Participants by arm
| Arm | Count |
|---|---|
| Belatacept 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.
Belatacept | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | Belatacept |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Region of Enrollment United States | 6 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 6 |
| other Total, other adverse events | 6 / 6 |
| serious Total, serious adverse events | 1 / 6 |
Outcome results
Primary
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
Time frame: Baseline and 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Belatacept | Change From Baseline in Serum Estimated Glomerular Filtration Rate (eGFR) | 2.25 ml/min/1.73m2 | Standard Deviation 3.35 |
Primary
Serum Creatinine at Year 1
Serum Creatinine measured at 1 year after conversion from Tacrolimus to Belatacept.
Time frame: 1 year
Population: 4 subjects who completed 1 year of Belatacept were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Belatacept | Serum Creatinine at Year 1 | 1.8 mg/dl | Standard Deviation 0.2 |
Secondary
Change From Baseline Serum Hemoglobin A1c
Pancreas Transplant Function was measured by assessing change in Pre HbA1c to Post HbA1c at1 year after conversion.
Time frame: Baseline and 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Belatacept | Change From Baseline Serum Hemoglobin A1c | 5.9 percentage of glycosylated hemoglobin | Standard Deviation 0.15 |
Secondary
Number of Participants With Pancreas Transplant Rejection
Pancreas Rejection as measured by serum amylase, serum lipase.
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Belatacept | Number of Participants With Pancreas Transplant Rejection | 2 Participants |
Secondary
Pancreas Transplant Function as Measured by Fasting Serum Glucose Level.
Fasting Serum Glucose level measured at 1 year after conversion from Tacrolimus to Belatacept.
Time frame: 1 Year
Population: 4 subjects who completed 1 year of Belatacept.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Belatacept | Pancreas Transplant Function as Measured by Fasting Serum Glucose Level. | 96.9 mg/dl | Standard Deviation 6.3 |