Clinical trial NCT05836636: Immune Monitoring of Prevalent Kidney Transplant Recipients Using Torque Teno Virus: A Single-Center, Prospective Cohort Study
Official title: Immune Monitoring of Prevalent Kidney Transplant Recipients Using Torque Teno Virus: A Single-Center, Prospective Cohort Study
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Kidney Transplant Infection
Kidney Transplant Rejection
Kidney Transplant; Complications
Lead sponsor: Singapore General Hospital
Sponsor class: OTHER
First posted: 2023-05-01
Enrollment: 172
Sex: ALL
Minimum age (years): 21
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Kidney transplant recipients (KTRs) on stable doses of immunosuppression for more than 3 months

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.


Eligibility criteria: 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

Primary outcomes:
measure: Severe infections defined as any infection requiring hospitalization
timeFrame: 1 year
Secondary outcomes:
measure: Opportunistic infections
timeFrame: 1 year
measure: De novo malignancy
timeFrame: 1 year
measure: Calcineurin inhibitor nephrotoxicity (biopsy-proven)
timeFrame: 1 year
measure: Rejection (biopsy-proven)
timeFrame: 1 year
measure: Glomerulonephritis - de novo or recurrent (biopsy-proven)
timeFrame: 1 year
measure: Graft function
timeFrame: 1 year
measure: Graft loss
timeFrame: 1 year
measure: Mortality
timeFrame: 1 year
measure: Immunosuppression-related adverse event
timeFrame: 1 year
measure: Immune-mediated adverse event
timeFrame: 1 year
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: Singapore General Hospital
Study officials:
References: