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

Kidney Transplantation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01771705
• Other study ID #: NFAT dependent cytokines
• Status: Completed
• Phase: N/A
• Start date: May 2, 2013
• Est. completion date: April 17, 2017

Study information

• Verified date: May 2020
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: April 17, 2017
• Est. primary completion date: August 13, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Kidney Transplantation

Intervention

Other:
• Dose adjust group (NFAT)
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%.

Locations

Country	Name	City	State
United States	University of California, San Francisco	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	Astellas Pharma Inc

Country where clinical trial is conducted

United States, 

References & Publications (7)

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. — View 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. — View 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. T — View Citation

Hartmann B, Schmid G, Graeb C, Bruns CJ, Fischereder M, Jauch KW, Heeschen C, Guba M. Biochemical monitoring of mTOR inhibitor-based immunosuppression following kidney transplantation: a novel approach for tailored immunosuppressive therapy. Kidney Int. 2 — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	•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	1 year (18 months post-transplant) biopsy proven acute rejections episodes		12 Months
Secondary	1 year (18 months post-transplant) cumulative infectious complications		12 Months
Secondary	1 year (18 months post-transplant) GFR		12 Months
Secondary	1 year (18 months post-transplant) allograft survival		12 Months
Secondary	1 year (18 months post-transplant) patient survival		12 Months