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

Immunosuppression Clinical Trial

— TTV  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05727709
• Other study ID #: CTTV study
• Status: Recruiting
• Start date: March 15, 2023
• Est. completion date: June 30, 2024

Study information

• Verified date: August 2023
• Source: Tongji Hospital
• Contact: Gang Chen, PhD
• Phone: +8613006187015
• Email: gchen[@]tjh.tjmu.edu.cn
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 220
• Est. completion date: June 30, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Immunosuppression
• Infections
• Kidney Transplant Infection
• Kidney Transplant Rejection
• Virus

Locations

Country	Name	City	State
China	West China Hospital,Sichuan University	Chengdu
China	The First Affiliated Hospital of Zhejiang University	Hangzhou
China	Changhai Hospital affiliated to Naval Military Medical University	Shanghai
China	Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology	Wuhan
China	the First Affiliated Hospital of Xi'an Jiaotong University	Xi'an

Sponsors (4)

Lead Sponsor	Collaborator
Tongji Hospital	Anapure BioScience, Caibo MedTech, SKM BioTech

Country where clinical trial is conducted

China, 

References & Publications (10)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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