Clinical trial NCT05727709: Dynamic Changes of Torquetenovirus (TTV) Load in Chinese Renal Transplant Recipients
Official title: Dynamic Changes of Torquetenovirus Load in Chinese Renal Transplant Recipients During Immunosuppressive Therapy: A Double-blind Multicenter Prospective Observational Cohort Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Kidney Transplant Rejection
Kidney Transplant Infection
Virus
Immunosuppression
Keywords: kidney transplantation
rejection
infection
donor specific antibodies
cell-free DNA
Torque Teno Virus
immuno-monitoring
Lead sponsor: Tongji Hospital
Sponsor class: OTHER
Collaborators: name: Anapure BioScience
name: Caibo MedTech
name: SKM BioTech
First posted: 2023-02-14
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study is designed as a national multi-center prospective observational double-blind cohort study. The main outcome measures are plasma Torque Teno Virus (TTV) load and the incidence of infection and acute rejection, which will be observed from day 1 before renal transplantation to 1 year after renal transplantation.The study population is renal transplant recipients. Double-blind refers to that both the medical staff in charge and the patients are blinded to the plasma TTV viral load at each follow-up visit, and this will be unblinded after the last follow-up visit of the last subject is completed.

Brief summary: The goal of this observational study is to learn about dynamic changes of Torquetenovirus (TTV) load in Chinese renal transplant recipients. The main questions it aims to answer are:

* Is there correlation between TTV load and rejection?
* Is there correlation between TTV load and infection?
* Can changes in the TTV load of kidney transplant recipients predict rejection or infection?

Participants will:

* receive 13 follow-up visits within 1 year after kidney transplantation
* provide 2 ml of whole blood for TTV load testing and other related testing at each follow-up
* provide 10 ml of whole blood for dd-cfDNA testing at four follow-ups (1, 3, 6 and 12 months after transplantation)
* provide 1 ml of serum for donor-specific antibody testing at three follow-ups (1, 6 and 12 months after transplantation)


Eligibility criteria: Inclusion Criteria:

* Receiving ABO compatible renal allotransplantation from the initiation of the study to December 31, 2023
* Receiving tacrolimus /mycophenolate mofetil(or mycophenolic acid)/prednisone as maintenance immunosuppression after renal transplantation
* Receiving universal prophylaxis for CMV infection and PJP infection

Exclusion Criteria:

* Receiving combined liver-kidney, pancreas-kidney or heart-kidney transplantation
* Recipients with active hepatitis B or hepatitis C infection
* Recipients with anticipated irregular follow-up

Primary outcomes:
measure: Renal allograft biopsy and serum creatinine
timeFrame: From day0 to day365 after kidney transplantation
Secondary outcomes:
measure: Infection event
timeFrame: From day0 to day365 after kidney transplantation
measure: donor-specific antibodies (DSA)
timeFrame: From day0 to day365 after kidney transplantation
measure: donor derived cell-free DNA
timeFrame: From day0 to day365 after kidney transplantation
Other outcomes:
Locations:
city: Chengdu
country: China
facility: West China Hospital，Sichuan University
city: Hangzhou
country: China
facility: The First Affiliated Hospital of Zhejiang University
city: Shanghai
country: China
facility: Changhai Hospital affiliated to Naval Military Medical University
city: Wuhan
country: China
facility: Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology
city: Xi'an
country: China
facility: the First Affiliated Hospital of Xi'an Jiaotong University
Study officials:
affiliation: Tongji Hospital
name: Gang Chen, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fishman JA. Opportunistic infections--coming to the limits of immunosuppression? Cold Spring Harb Perspect Med. 2013 Oct 1;3(10):a015669. doi: 10.1101/cshperspect.a015669.
citation: Haas M, Loupy A, Lefaucheur C, Roufosse C, Glotz D, Seron D, Nankivell BJ, Halloran PF, Colvin RB, Akalin E, Alachkar N, Bagnasco S, Bouatou Y, Becker JU, Cornell LD, Duong van Huyen JP, Gibson IW, Kraus ES, Mannon RB, Naesens M, Nickeleit V, Nickerson P, Segev DL, Singh HK, Stegall M, Randhawa P, Racusen L, Solez K, Mengel M. The Banff 2017 Kidney Meeting Report: Revised diagnostic criteria for chronic active T cell-mediated rejection, antibody-mediated rejection, and prospects for integrative endpoints for next-generation clinical trials. Am J Transplant. 2018 Feb;18(2):293-307. doi: 10.1111/ajt.14625. Epub 2018 Jan 21.
citation: Ahlenstiel-Grunow T, Pape L. Novel ways to monitor immunosuppression in pediatric kidney transplant recipients-underlying concepts and emerging data. Mol Cell Pediatr. 2021 Jul 26;8(1):8. doi: 10.1186/s40348-021-00118-8.
citation: De Vlaminck I, Khush KK, Strehl C, Kohli B, Luikart H, Neff NF, Okamoto J, Snyder TM, Cornfield DN, Nicolls MR, Weill D, Bernstein D, Valantine HA, Quake SR. Temporal response of the human virome to immunosuppression and antiviral therapy. Cell. 2013 Nov 21;155(5):1178-87. doi: 10.1016/j.cell.2013.10.034.
citation: Maggi F, Focosi D, Statzu M, Bianco G, Costa C, Macera L, Spezia PG, Medici C, Albert E, Navarro D, Scagnolari C, Pistello M, Cavallo R, Antonelli G. Early Post-Transplant Torquetenovirus Viremia Predicts Cytomegalovirus Reactivations In Solid Organ Transplant Recipients. Sci Rep. 2018 Oct 19;8(1):15490. doi: 10.1038/s41598-018-33909-7.
citation: Rezahosseini O, Drabe CH, Sorensen SS, Rasmussen A, Perch M, Ostrowski SR, Nielsen SD. Torque-Teno virus viral load as a potential endogenous marker of immune function in solid organ transplantation. Transplant Rev (Orlando). 2019 Jul;33(3):137-144. doi: 10.1016/j.trre.2019.03.004. Epub 2019 Apr 4.
citation: Solis M, Velay A, Gantner P, Bausson J, Filipputtu A, Freitag R, Moulin B, Caillard S, Fafi-Kremer S. Torquetenovirus viremia for early prediction of graft rejection after kidney transplantation. J Infect. 2019 Jul;79(1):56-60. doi: 10.1016/j.jinf.2019.05.010. Epub 2019 May 14.
citation: Focosi D, Maggi F. Torque teno virus monitoring in transplantation: The quest for standardization. Am J Transplant. 2019 May;19(5):1599-1601. doi: 10.1111/ajt.15194. Epub 2018 Dec 17. No abstract available.
citation: Kulifaj D, Durgueil-Lariviere B, Meynier F, Munteanu E, Pichon N, Dube M, Joannes M, Essig M, Hantz S, Barranger C, Alain S. Development of a standardized real time PCR for Torque teno viruses (TTV) viral load detection and quantification: A new tool for immune monitoring. J Clin Virol. 2018 Aug;105:118-127. doi: 10.1016/j.jcv.2018.06.010. Epub 2018 Jun 11.
citation: Fernandez-Ruiz M, Albert E, Gimenez E, Rodriguez-Goncer I, Andres A, Navarro D, Aguado JM. Early kinetics of Torque Teno virus DNA load and BK polyomavirus viremia after kidney transplantation. Transpl Infect Dis. 2020 Apr;22(2):e13240. doi: 10.1111/tid.13240. Epub 2020 Jan 9. No abstract available.