TTV-based mAnagement Of Long-term ImmunosuppreSsion in Kidney Transplantation (TAOIST)

May 22, 2026 updated by: Hospices Civils de Lyon

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

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 six 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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

600

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Bordeaux (France), France, 33000
        • Not yet recruiting
        • Service de Néphrologie-Transplantation-Dialyse I Hôpital Pellegrin I - CHU Bordeaux
        • Contact:
      • Lyon, France, 69003
        • Recruiting
        • Service de transplantation, néphrologie et immunologie clinique Hospices Civils de Lyon, Hôpital Edouard Herriot
        • Contact:
        • Principal Investigator:
          • Olivier THAUNAT, Professor
      • Strasbourg (france), France, 67091
        • Not yet recruiting
        • Service de Néphrologie, Dialyse et Transplantation Rénale Nouvel Hôpital Civil
        • Contact:
      • Toulouse (France), France, 31059
        • Recruiting
        • Département de Néphrologie et Transplantation d'Organes Hôpital Rangueil - CHU de Toulouse
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • Recipient of an HLA identical graft
  • Mutiple organ transplantation or functional transplant other than kidney
  • Maintenance immunosuppression that includes a mTOR inhibitor, belatacept or imurel
  • Presence of histological sign of active rejection (i+t > 2 and g+cpt > 2) on graft biopsy performed within 3 months before enrollment
  • Uncontrolled infection at inclusion
  • Infection requiring hospitalization within 3 months before inclusion
  • Diagnosis of a cancer of interest between the (current) transplantation and inclusion
  • Pregnant, unwillingness to practice adequate contraception or patient with a pregnancy plan during 3 years of study
  • Person not affiliated to a social security scheme or beneficiary of a similar scheme
  • Person subject to a legal protection measure (guardianship, curatorship) or deprived of liberty

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 6 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: EQ-5D-5L questionnaire
Completed every 6 months and each time a complication of interest occurs
Biological: Biological tests
Biological tests as routine care procedure (creatinine, CNI pre-dose trough level) will be performed every 6 months
Biological: TTV DNAemia
Every 6 months, one sample added at the same time (7mL) of a routine laboratory analysis for TTV DNAemia
Other: Standard Immunosuppression
TTV DNAemia will also be measured every 6 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.
Other: EQ-5D-5L questionnaire
Completed every 6 months and each time a complication of interest occurs
Biological: Biological tests
Biological tests as routine care procedure (creatinine, CNI pre-dose trough level) will be performed every 6 months
Biological: TTV DNAemia
Every 6 months, one sample added at the same time (7mL) of a routine laboratory analysis for TTV DNAemia

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Compare the time from randomization to first complication of inadequate immunosuppression between the experimental group, whose treatment is tailored on quarterly TTV viral load results, and the control group.
Time Frame: through study completion, an average of 6 years
Time from randomization to occurrence of the first complication of inadequate immunosuppression: development of dnDSA, biopsy-proven rejection, infection, cancer, graft loss. Patients lost to follow-up or died without an event before will be right censored at this date.
through study completion, an average of 6 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of patients with at least one complication of inadequate immunosuppression between the experimental and control groups at 36 months
Time Frame: through study completion, an average of 6 years
Percentage of patients with at least one complication of inadequate immunosuppression during the 36 months of follow-up.
through study completion, an average of 6 years
Compare the rate of complications of inadequate immunosuppression between patients in the experimental and control groups.
Time Frame: through study completion, an average of 6 years
Number of complications of inadequate immunosuppression/patient/month of follow-up
through study completion, an average of 6 years
Describe the nature and timing of various complications of inadequate immunosuppression in the experimental and control groups.
Time Frame: through study completion, an average of 6 years
Percentage of patients (at 36 months) and time to first complication for each of the complications of interest: development of dnDSA, biopsy-proven rejection, infection, cancer, graft loss.
through study completion, an average of 6 years
Compare the proportion of patients with adequate immunosuppressive therapy between the experimental and control groups.
Time Frame: through study completion, an average of 6 years
Percentage of patients with TTV viral load between 3.8 and 5.1 log cp/ml at the majority (>6/12) of quarterly routine controls.
through study completion, an average of 6 years
Evaluate how nephrologists and biologists feel about using the new test in clinical practice.
Time Frame: 6th year
Questionnaires specific to each sub-populations (nephrologists and biologists) using open-ended questions and Likert scale-coded responses.
6th year
Assess the cost-effectiveness of the intervention compared to standard care at 36 months from the French Health care System perspective
Time Frame: through study completion, an average of 6 years
Cost-effectiveness ratio (ICER) is defined as the difference in cost between the intervention and the standard care, divided by the difference in their effect (QALY).
through study completion, an average of 6 years
Compare the proportion of quarterly systematic checks of TTV DNAemia in the target between patients in the experimental and control groups.
Time Frame: Every 6 months
Percentage of quarterly routine TTV viral load tests between 3.8 and 5.1 log cp/ml.
Every 6 months
Model the impact of variations in dose and residual rates (pre-dose trough levels or AUC) of the various immunosuppressive drugs on TTV viral load.
Time Frame: every 6 months
Joint analysis of the evolution of dose variations, residual immunosuppression rates of immunosuppressive drugs and TTV viral load.
every 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospices Civils de Lyon

Collaborators

BioMérieux

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 23, 2025

Primary Completion (Estimated)

May 1, 2028

Study Completion (Estimated)

February 2, 2031

Study Registration Dates

First Submitted

February 3, 2025

First Submitted That Met QC Criteria

February 11, 2025

First Posted (Actual)

February 17, 2025

Study Record Updates

Last Update Posted (Actual)

May 27, 2026

Last Update Submitted That Met QC Criteria

May 22, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 69HCL23_0834

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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