Personalization of Maintenance Immunosuppression Based on TTV Viral Load to Prevent Long-term Complications in Renal Transplantation

Status: Recruiting
Location: See all (4) locations...
Intervention Type: Other, Biological
Study Type: Interventional
Study Phase: Not Applicable
SUMMARY

Long-term outcomes in kidney transplantation remain a significant challenge, as complications such as donor-specific antibodies (DSA), antibody-mediated rejection, infections, and cancer increasingly threaten graft and patient survival over time. The development of non-invasive biomarkers to guide the management of therapeutic immunosuppression beyond the first year post-transplantation is therefore a crucial unmet need. Torque Teno Virus (TTV), a non-pathogenic virus with a high prevalence worldwide, has emerged as a promising biomarker in this context. Its replication inversely reflects immune control by T cells, correlating with the depth of therapeutic immunosuppression. Additionally, its slow replication kinetics make TTV DNAemia a useful marker for evaluating patient adherence to immunosuppressive treatments. The TAOIST study tests whether longitudinal monitoring of TTV DNAemia every three months, starting from the second year after transplantation, can guide the personalization of immunosuppressive therapy. The primary endpoint is the time to the first occurrence of complications linked to inadequate immunosuppression, including dnDSA, biopsy-proven rejection, infection, cancer, or graft loss. Secondary objectives include evaluating the acceptability of TTV DNAemia among healthcare professionals and assessing its cost-effectiveness compared to standard care. An ancillary objective examines the link between TTV DNAemia and the immunosuppressant possession ratio (IPR) to explore its potential as a marker of treatment adherence.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• Adult ≥ 18 years-old

• Recipient of a kidney allograft (third graft at most)

• 12 to 48 months post-transplantation

• Stable graft function (defined as: delta creatininemia over the previous 6 months \< 20% and proteinuria \< 30mg/mmol)

• On maintenance immunosuppression, which includes CNI (cyclosporin or tacrolimus) and MMF (Cellcept or Myfortic) with or without corticosteroids

• Detectable TTV DNAemia at enrollment

• No circulating DSA in solid phase assay

• Undetectable BKV DNAemia at enrollment

• Written informed consent

Locations
Other Locations
France
Service de Néphrologie-Transplantation-Dialyse I Hôpital Pellegrin I - CHU Bordeaux
NOT_YET_RECRUITING
Bordeaux (france)
Service de transplantation, néphrologie et immunologie clinique Hospices Civils de Lyon, Hôpital Edouard Herriot
RECRUITING
Lyon
Service de Néphrologie, Dialyse et Transplantation Rénale Nouvel Hôpital Civil
NOT_YET_RECRUITING
Strasbourg (france)
Département de Néphrologie et Transplantation d'Organes Hôpital Rangueil - CHU de Toulouse
NOT_YET_RECRUITING
Toulouse (france)
Contact Information
Primary
Olivier THAUNAT, Professor MD, PhD
olivier.thaunat@chu-lyon.fr
+334.72.11.69.28
Time Frame
Start Date: 2025-04-23
Estimated Completion Date: 2031-02-02
Participants
Target number of participants: 300
Treatments
Experimental: TTV-guided immunosuppression
The adaptation of the dose of maintenance immunosuppressive drugs will be based on TTV DNAemia measured on site in the plasma of patients every 3 months (at distance of an infection or a vaccination). The physicians will be free to change the dose of calcineurin inhibitors (CNI) and/or the mycophenolate mofetil (MMF) to maintain TTV DNAemia between 3.8 and 5.1 log10 cp/mL as long as the trough levels remain between 3-12 ng/mL for tacrolimus (50-250 ng/mL for cyclosporin) and the daily dose of MMF is comprise between 250 and 1500 mg bid for Cellcept (180 and 900 mg for Myfortic).
Other: Standard Immunosuppression
TTV DNAemia will also be measured every 3 months but the results will not be communicated to the physicians. Instead, the adaptation of the dose of maintenance immunosuppressive drugs will be performed according to the current standard of care: i) the dose of the CNI will be adapted to maintain the trough levels, monitored in the circulation every 3 month, between 5-10 ng/mL for tacrolimus (75-150 ng/mL for cyclosporin) and ii) the dose of MMF will be adjusted to maintain the AUC, measured every year, between 30-60 h.mg/L.
Sponsors
Collaborators: BioMérieux
Leads: Hospices Civils de Lyon

This content was sourced from clinicaltrials.gov