NFAT-Dependent Cytokine Gene Expression for Immune Monitoring in Kidney Transplant Patients

Study Overview
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Brief Summary
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The purpose of this study is to compare two different ways of monitoring the immune system to determine how to manage the doses of anti-rejection medications.

Detailed Description
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This is a single center randomized controlled trial investigating the efficacy and safety of adjusting calcineurin inhibitor (CNI) dosing based on Nuclear Factor of Activating T Cells (NFAT)-dependent cytokine gene expression as compared to standard of care adjustments based on trough level. Before any study-related evaluations are performed, the patient must give written informed consent. Once consent is obtained, a patient's eligibility to participate in the study will be assessed within 4 weeks of their 6 month management biopsy. Approximately 40 patients who meet inclusion criteria will be randomized at University of California, San Francisco (UCSF). Eligible patients include any patient maintained on triple therapy with tacrolimus, mycophenolate mofetil ,and prednisone who has had no prior rejection episodes and who has undergone a 6 month management kidney biopsy that shows no evidence of acute cellular rejection or antibody mediated rejection.

Official Title
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NFAT-Dependent Cytokine Gene Expression for Immune Monitoring in Kidney Transplant Patients

Conditions
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Kidney Transplantation

Intervention / Treatment
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* Other: Dose adjust group (NFAT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligible patients include any patient maintained on triple therapy with tacrolimus, mycophenolate mofetil ,and prednisone who has had no prior rejection episodes and who has undergone a 6 month management kidney biopsy that shows no evidence of acute cellular rejection or antibody mediated rejection. Exclusion Criteria: Any patient not maintained on triple therapy with tacrolimus, mycophenolate mofetil and steroids and/or who had evidence of rejection on 6- month management biopsy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose adjust group (NFAT)<br>Within 4 weeks of a 6 month management biopsy, if eligibility is confirmed, NFAT dependent cytokines including IL-2, IFNg, and GMCSF at times C0 and C1.5 will be performed with the residual expression calculated based on the ratio of C1.5/C0 x 100%. If the average residual expression of the 3 cytokines is <20%, the CNI daily dose will be reduced by 15%. If the average residual gene expression of the 3 cytokines is > 60% the CNI daily dose will be increased by 15%. | Other: Dose adjust group (NFAT)<br>* If the average residual expression of the 3 cytokines is <20%, the CNI daily dose will be reduced by 15%. If the average residual gene expression of the 3 cytokines is > 60% the CNI daily dose will be increased by 15%.<br>|
| No Intervention: Standard of care group<br>A CNI trough level will be obtained. Adjustments of CNI will be based on target trough drug levels as per standard of care. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| •Number of adjustments made to tacrolimus regimen at 6 months; •Lack of correlation between NFAT-dependent cytokine expression and tacrolimus trough levels |  | 6 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1 year (18 months post-transplant) biopsy proven acute rejections episodes |  | 12 Months | 
| 1 year (18 months post-transplant) cumulative infectious complications |  | 12 Months | 
| 1 year (18 months post-transplant) GFR |  | 12 Months | 
| 1 year (18 months post-transplant) allograft survival |  | 12 Months | 
| 1 year (18 months post-transplant) patient survival |  | 12 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transplantation, Kidney, calcineurin inhibitor, NFAT, tacrolimus