Clinical trial NCT01771705: NFAT-Dependent Cytokine Gene Expression for Immune Monitoring in Kidney Transplant Patients
Official title: NFAT-Dependent Cytokine Gene Expression for Immune Monitoring in Kidney Transplant Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Kidney Transplantation
Keywords: Transplantation
Kidney
calcineurin inhibitor
NFAT
tacrolimus
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Astellas Pharma Inc
First posted: 2013-01-18
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: •Number of adjustments made to tacrolimus regimen at 6 months; •Lack of correlation between NFAT-dependent cytokine expression and tacrolimus trough levels
timeFrame: 6 Months
Secondary outcomes:
measure: 1 year (18 months post-transplant) biopsy proven acute rejections episodes
timeFrame: 12 Months
measure: 1 year (18 months post-transplant) cumulative infectious complications
timeFrame: 12 Months
measure: 1 year (18 months post-transplant) GFR
timeFrame: 12 Months
measure: 1 year (18 months post-transplant) allograft survival
timeFrame: 12 Months
measure: 1 year (18 months post-transplant) patient survival
timeFrame: 12 Months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Flavio Vincenti, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Francisco
name: Allison Webber, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Giese T, Sommerer C, Zeier M, Meuer S. Monitoring immunosuppression with measures of NFAT decreases cancer incidence. Clin Immunol. 2009 Sep;132(3):305-11. doi: 10.1016/j.clim.2009.03.520. Epub 2009 Apr 23.
citation: Giese T, Zeier M, Schemmer P, Uhl W, Schoels M, Dengler T, Buechler M, Meuer S. Monitoring of NFAT-regulated gene expression in the peripheral blood of allograft recipients: a novel perspective toward individually optimized drug doses of cyclosporine A. Transplantation. 2004 Feb 15;77(3):339-44. doi: 10.1097/01.TP.0000109260.00094.01.
citation: Sommerer C, Giese T, Schmidt J, Meuer S, Zeier M. Ciclosporin A tapering monitored by NFAT-regulated gene expression: a new concept of individual immunosuppression. Transplantation. 2008 Jan 15;85(1):15-21. doi: 10.1097/01.tp.0000296824.58884.55.
citation: Sommerer C, Zeier M, Meuer S, Giese T. Individualized monitoring of nuclear factor of activated T cells-regulated gene expression in FK506-treated kidney transplant recipients. Transplantation. 2010 Jun 15;89(11):1417-23. doi: 10.1097/TP.0b013e3181dc13b6.
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citation: Leogrande D, Teutonico A, Ranieri E, Saldarelli M, Gesualdo L, Schena FP, Di Paolo S. Monitoring biological action of rapamycin in renal transplantation. Am J Kidney Dis. 2007 Aug;50(2):314-25. doi: 10.1053/j.ajkd.2007.05.002.
citation: Belouski SS, Wilkinson J, Thomas J, Kelley K, Wang SW, Suggs S, Ferbas J. Utility of lyophilized PMA and ionomycin to stimulate lymphocytes in whole blood for immunological assays. Cytometry B Clin Cytom. 2010 Jan;78(1):59-64. doi: 10.1002/cyto.b.20492.