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

NCT02278952 | Completed Results

• 1 other identifier: Astellas ISR000990
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Transplantation, Lung

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (3)

• Association of Percentage of Mean Residual Expression (MRE%) of NFAT-related Cytokine Expression and Weeks Post-Transplant

  from 1 month (4 weeks) up to 18 months (82 weeks) post-transplant

• Association of Percentage of Mean Residual Expression (MRE%) of NFAT-related Cytokine Expression and Tacrolimus Trough Level

  from 1 month up to 18 months post-transplant

• Association of Percentage of Mean Residual Expression (MRE%) of NFAT-related Cytokine Expression and Medication Dosages

  from 1 month up to 18 months post-transplant

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Lung transplant recipients

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Astellas Scientific & Medical Affairs, Inc.: collaborator

Study Sites (1)

University of California

San Francisco, California, 94143, United States

Location

Limitations and Caveats

Higher than expected variance in MRE and missed study visits somewhat reduced statistical power.

Results Point of Contact

• Title: Dr. John Greenland
• Organization: University of California, San Francisco

john.greenland@ucsf.edu

415-476-0789

Study Officials

• Greenland John, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2014
• First Posted: October 30, 2014
• Study Start: December 1, 2014
• Primary Completion: May 1, 2017
• Study Completion: January 1, 2018
• Last Updated: December 3, 2019
• Results First Posted: December 3, 2019

Record last verified: 2019-11

Locations

US (1)