Dynamic Changes of Torquetenovirus (TTV) Load in Chinese Renal Transplant Recipients (TTV)

Dynamic Changes of Torquetenovirus Load in Chinese Renal Transplant Recipients During Immunosuppressive Therapy: A Double-blind Multicenter Prospective Observational Cohort Study

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)

Study Overview

• Status: Recruiting
• Conditions: Kidney Transplant Infection; Kidney Transplant Rejection; Immunosuppression; Virus

• Study Type: Observational
• Enrollment (Estimated): 220

Contacts and Locations

• Study Contact: Name: Gang Chen, PhD; Phone Number: +8613006187015; Email: gchen@tjh.tjmu.edu.cn
• Study Contact Backup: Name: Lan Zhu, MD; Email: zhulan@tjh.tjmu.edu.cn

Study Locations

• China
  • Chengdu, China
    • Recruiting
    • West China Hospital,Sichuan University
    • Contact: Tao Lin, PhD; Phone Number: 18980602093; Email: dr_taolin@163.com
    • Principal Investigator: Tao Lin, Dr.
  • Hangzhou, China
    • Recruiting
    • The First Affiliated Hospital of Zhejiang University
    • Contact: Jianyong Wu; Phone Number: 86-13906523095; Email: wujianyong1964@zju.edu.cn
  • Shanghai, China
    • Recruiting
    • Changhai Hospital affiliated to Naval Military Medical University
    • Contact: Lei Zhang; Phone Number: 86-21-31162862; Email: zl3514@139.com
  • Wuhan, China, 430030
    • Recruiting
    • Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology
    • Contact: Lan Zhu; Phone Number: 86-27-83662882; Email: zhulan@tjh.tjmu.edu.cn
  • Xi'an, China
    • Recruiting
    • The First Affiliated Hospital of Xi'An JiaoTong University
    • Contact: Jin Zheng, PhD; Phone Number: 86-29-85323721; Email: jzheng@xjtu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• 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.

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal allograft biopsy and serum creatinine	Any biopsy-proven acute rejection (Banff criterea) and clinical diagnosed acute rejection	From day0 to day365 after kidney transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infection event	Any bacterial, fungal (including PJP), mycobacterial, or viral (including CMV viremia, EB viremia, BK Viremia, BK Viruria, etc.) infection requiring hospitalization or prolongation of hospitalization, or requiring intravenous antibiotics or therapeutic use of antiviral drugs, or requiring reduction of immunosuppressive drugs	From day0 to day365 after kidney transplantation
donor-specific antibodies (DSA)	the development of de novo DSA or a 30% increase of MFI value in preformed DSA	From day0 to day365 after kidney transplantation
donor derived cell-free DNA	An increase in absolute or percent donor derived-cell free DNA from 1 month post-transplant	From day0 to day365 after kidney transplantation

Collaborators and Investigators

• Sponsor: Tongji Hospital
• Collaborators: Anapure BioScience; Caibo MedTech; SKM BioTech
• Investigators: Principal Investigator: Gang Chen, PhD, Tongji Hospital

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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. Erratum In: Mol Cell Pediatr. 2021 Sep 30;8(1):14.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2023
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: February 5, 2023
• First Submitted That Met QC Criteria: February 5, 2023
• First Posted (Actual): February 14, 2023

Study Record Updates

• Last Update Posted (Actual): August 22, 2023
• Last Update Submitted That Met QC Criteria: August 21, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: kidney transplantation; rejection; infection; cell-free DNA; donor specific antibodies; Torque Teno Virus; immuno-monitoring
• Additional Relevant MeSH Terms: Infections
• Other Study ID Numbers: CTTV study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: all IPD that underlie results in a publication
• IPD Sharing Time Frame: Data requests can be submitted starting 9 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis
• IPD Sharing Access Criteria: Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information or to submit a request, please contact tongjihlunli@163.com
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No