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

Kidney Transplant; Complications Clinical Trial

— TTV-KTR-SGH  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05836636
• Other study ID #: 2023/2170
• Status: Recruiting
• Start date: June 27, 2023
• Est. completion date: March 31, 2025

Study information

• Verified date: July 2023
• Source: Singapore General Hospital
• Contact: Quan Yao Ho, MBBS, MRCP, MMed, FAMS
• Phone: 6563214436
• Email: ho.quan.yao[@]singhealth.com.sg
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 172
• Est. completion date: March 31, 2025
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Kidney Transplant Infection
• Kidney Transplant Rejection
• Kidney Transplant; Complications

Intervention

Other:
• Torque teno virus DNA measurement
Torque teno virus DNA level will be obtained from all study subjects upon recruitment, when subjects are admitted and when subjects undergo kidney allograft biopsies.

Locations

Country	Name	City	State
Singapore	Singapore General Hospital	Singapore

Sponsors (1)

Lead Sponsor	Collaborator
Singapore General Hospital

Country where clinical trial is conducted

Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Severe infections defined as any infection requiring hospitalization	Any infection requiring hospitalization	1 year
Secondary	Opportunistic infections	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)	1 year
Secondary	De novo malignancy	De novo malignancy	1 year
Secondary	Calcineurin inhibitor nephrotoxicity (biopsy-proven)	Calcineurin inhibitor nephrotoxicity (biopsy-proven)	1 year
Secondary	Rejection (biopsy-proven)	With and without borderline T cell-mediated rejection	1 year
Secondary	Glomerulonephritis - de novo or recurrent (biopsy-proven)		1 year
Secondary	Graft function	serum creatinine, estimated glomerular filtration rate by the CKD-EPI equation and urine protein-to-creatinine ratio	1 year
Secondary	Graft loss	Censored and non-censored for death	1 year
Secondary	Mortality	All-cause and cause-specific - i.e., infection, malignancy, cardiovascular, others	1 year
Secondary	Immunosuppression-related adverse event	Composite outcome of severe infections defined as any infection requiring hospitalization, opportunistic infections, de novo malignancy and calcineurin inhibitor nephrotoxicity	1 year
Secondary	Immune-mediated adverse event	Composite outcome of rejection (biopsy-proven) and glomerulonephritis (biopsy-proven)	1 year