TTV-KTR-SGH: Immune Monitoring of Prevalent Kidney Transplant Recipients Using Torque Teno Virus: A Single-Center, Prospective Cohort Study

Sponsor

Singapore General Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05836636

Collaborator

(none)

172

Enrollment

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Kidney transplant recipients (KTRs) suffer from immunosuppression-related adverse events (iRAEs), such as infections and malignancy from chronic immunosuppression exposure but are also at risk of graft loss from rejection with under-immunosuppression. Biomarkers that predict both iRAEs and rejection and allow individualisation of immunosuppression exposure are lacking. While plasma viral DNA levels of Torque Teno Virus (TTV), a widely prevalent, non-pathogenic virus, have been shown to predict both iRAE and rejection in incident KTRs within 1 year after transplant, its role for prevalent KTRs on stable immunosuppression is unclear.

The investigators hypothesise that plasma TTV levels can predict iRAEs and rejection in KTRs on stable immunosuppression and propose a pilot study to pursue three specific aims: (1) To determine the TTV levels and its relationship with clinical factors affecting the 'net state of immunosuppression' in prevalent KTRs. (2) To analyse the prognostic value of TTV levels for iRAEs and rejection in prevalent KTRs. (3) To compare the prognostic performance of TTV levels to commonly available biomarkers and composite prognostic scores.

The investigators seek pursue these aims by performing a single-centre, prospective, observational cohort study of 172 KTRs on stable immunosuppression for more than 3 months. TTV levels will be measured, using the TTV R-GENE® kit, upon recruitment and when kidney allograft biopsies are performed. Subjects will be monitored for iRAEs and rejection for at least 12 months.

The study will provide data on the distribution of TTV levels in a prevalent cohort of KTRs and analyse its relationship with clinical factors and important clinical outcomes. If the study indicates that TTV may be predictive of iRAEs and rejection, the investigators aim to conduct further studies including interventional studies using TTV levels to guide immunosuppression. Ultimately, the investigators aim to use TTV as a biomarker to optimise long-term immunosuppression exposure, reduce the risk of iRAEs without increase in rejection, and improve long-term outcomes for KTRs.

Condition or Disease	Intervention/Treatment	Phase
Kidney Transplant Infection Kidney Transplant Rejection Kidney Transplant; Complications	Other: Torque teno virus DNA measurement

Study Design

Study Type:

Observational

Anticipated Enrollment :

172 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Immune Monitoring of Prevalent Kidney Transplant Recipients Using Torque Teno Virus: A Single-Center, Prospective Cohort Study

Anticipated Study Start Date :

Jun 1, 2023

Anticipated Primary Completion Date :

Mar 31, 2024

Anticipated Study Completion Date :

Mar 31, 2025

Outcome Measures

Primary Outcome Measures

Severe infections defined as any infection requiring hospitalization [1 year]
Any infection requiring hospitalization

Secondary Outcome Measures

Opportunistic infections [1 year]
intracellular bacteria, mycobacteria, Listeria monocytogenes, and Nocardia spp., herpesviruses (CMV, HSV, and VZV), polyomaviruses, yeasts (Candida and Cryptococcus), molds (invasive aspergillosis and mucormycosis), and parasites (Toxoplasma gondii, PJP, and Leishmania)
De novo malignancy [1 year]
De novo malignancy
Calcineurin inhibitor nephrotoxicity (biopsy-proven) [1 year]
Calcineurin inhibitor nephrotoxicity (biopsy-proven)
Rejection (biopsy-proven) [1 year]
With and without borderline T cell-mediated rejection
Glomerulonephritis - de novo or recurrent (biopsy-proven) [1 year]
Graft function [1 year]
serum creatinine, estimated glomerular filtration rate by the CKD-EPI equation and urine protein-to-creatinine ratio
Graft loss [1 year]
Censored and non-censored for death
Mortality [1 year]
All-cause and cause-specific - i.e., infection, malignancy, cardiovascular, others
Immunosuppression-related adverse event [1 year]
Composite outcome of severe infections defined as any infection requiring hospitalization, opportunistic infections, de novo malignancy and calcineurin inhibitor nephrotoxicity
Immune-mediated adverse event [1 year]
Composite outcome of rejection (biopsy-proven) and glomerulonephritis (biopsy-proven)

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Kidney transplant recipients on follow up at Singapore General Hospital (SGH)
More than 21 years old
On stable doses of immunosuppression for more than 3 months

Exclusion Criteria:

Titration of immunosuppression (e.g. for rejection or infection) less than 3 months ago
Active infection requiring treatment
Less than 21 years old
Unable to provide informed consent

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Singapore General Hospital

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Singapore General Hospital

ClinicalTrials.gov Identifier:

NCT05836636

Other Study ID Numbers:

2023/2170

First Posted:

May 1, 2023

Last Update Posted:

May 3, 2023

Last Verified:

May 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Study Results

No Results Posted as of May 3, 2023