Tacrolimus Adjustment by NFAT-related Gene Expression in Lung Allograft Recipients.

Transplantation, Lung Clinical Trial

— TANGELA  

Official title:

Tacrolimus Adjustment by NFAT-related Gene Expression in Lung Allograft Recipients.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02278952
• Other study ID #: Astellas ISR000990
• Status: Completed
• Start date: December 2014
• Est. completion date: January 2018

Study information

• Verified date: November 2019
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is a non-interventional cohort study to assess a novel assay to detect excessive or insufficient immunosuppression from the drug tacrolimus in lung transplant recipients. The assay measures mean residual expression (MRE) of genes downstream of nuclear factor of activated T cells (NFAT), a transcription factor regulated by tacrolimus. The investigators will assess whether MRE levels identify subjects at risk for rejection (insufficient immunosuppression) or infection (excessive immunosuppression).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: January 2018
• Est. primary completion date: May 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion criteria:

The study will include lung allograft recipients within 2 months of transplantation at UCSF.

Exclusion criteria:

Subjects will be excluded who are (a) unable to provide consent or (b) if treating clinicians do not anticipate subject will start on tacrolimus. Recruitment and enrollment in this study are targeted equally between women and minorities and the study will not exclude any gender or racial/ethnic group. This study does not involve vulnerable populations.

Related Conditions & MeSH terms

• Transplantation, Lung

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	Astellas Scientific & Medical Affairs, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Association of Percentage of Mean Residual Expression (MRE%) of NFAT-related Cytokine Expression and Acute Cellular Rejection	The prescribed tacrolimus dosage was determined by the treating physician who was not aware of the study-assay values. For the study assay, two blood draws were collected at a study visit during the assessment period (from 1 month up to 18 months post-transplant). The first draw occurred before tacrolimus dosage (trough) and the second occurred 90 to 120 minutes after tacrolimus dosage (peak). To determine MRE, whole blood was stimulated, RNA was extracted, and residual expression of NFAT-related cytokines (NFAT: nuclear factor of activated T-cells) was determined by quantitative polymerase chain reaction (qPCR). Researchers stratified blood draws based on subject's rejection pathology at time of blood draw and observed percentage distribution of MRE values within each rejection pathology group. Observed differences between MRE distributions within non-rejection group and rejection groups.	from 1 month up to 18 months post-transplant
Primary	Association of Percentage of Mean Residual Expression (MRE%) of NFAT-related Cytokine Expression and Infection	Researchers stratified blood draws based on subject's airway infection status at time of blood draw (based on biopsy results) and observed percentage distribution of MRE values within each infection status group. Researchers observed differences between MRE distributions within subjects with airway infection at time of blood draw and subjects with no infection diagnosis.	from 1 month up to 18 months post-transplant
Secondary	Association of Percentage of Mean Residual Expression (MRE%) of NFAT-related Cytokine Expression and Weeks Post-Transplant	Researchers observed percentage distribution of MRE values at time of blood draw from study visits at 4 weeks post-transplant up to 82 weeks post-transplant. Researchers observed association between percentage of MRE at time of blood draw and the number of weeks post-transplant.	from 1 month (4 weeks) up to 18 months (82 weeks) post-transplant
Secondary	Association of Percentage of Mean Residual Expression (MRE%) of NFAT-related Cytokine Expression and Tacrolimus Trough Level	Researchers observed percentage distribution of MRE values on the day of blood draws. Researchers measured tacrolimus concentration in blood drawn before tacrolimus dosage (trough) and observed the association between percentage of MRE on the day of blood draw and tacrolimus trough level.	from 1 month up to 18 months post-transplant
Secondary	Association of Percentage of Mean Residual Expression (MRE%) of NFAT-related Cytokine Expression and Medication Dosages	Researchers observed percentage distribution of MRE values on the day of blood draws and measured tacrolimus, prednisone, and mycophenolate dose at the time of blood draw. Researchers observed the association between percentage of MRE on the day of blood draw and tacrolimus, prednisone, and mycophenolate dose, respectively, at the time of blood draw.	from 1 month up to 18 months post-transplant