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

Sponsor

University of California, San Francisco (Other)

Overall Status

Completed

CT.gov ID

NCT01771705

Collaborator

Astellas Pharma Inc (Industry)

Enrollment

Location

Arms

47.5

Actual Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Kidney Transplantation	Other: Dose adjust group (NFAT)	N/A

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

May 2, 2013

Actual Primary Completion Date :

Aug 13, 2016

Actual Study Completion Date :

Apr 17, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose adjust group (NFAT) 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) 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%.
No Intervention: Standard of care group A CNI trough level will be obtained. Adjustments of CNI will be based on target trough drug levels as per standard of care.

Arm

Intervention/Treatment

Experimental: Dose adjust group (NFAT)

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)

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%.

No Intervention: Standard of care group

A CNI trough level will be obtained. Adjustments of CNI will be based on target trough drug levels as per standard of care.

Outcome Measures

Primary Outcome Measures

•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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, San Francisco	San Francisco	California	United States	94143

Sponsors and Collaborators

University of California, San Francisco
Astellas Pharma Inc

Investigators

Principal Investigator: Flavio Vincenti, M.D., University of California, San Francisco
Principal Investigator: Allison Webber, M.D., University of California, San Francisco