Clinical trial NCT06829719: TTV-based MAnagement of Long-term ImmunosuppreSsion in Kidney Transplantation
Official title: Personalization of Maintenance Immunosuppression Based on TTV Viral Load to Prevent Long-term Complications in Renal Transplantation
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Infection
Cancer
Rejection
Kidney Transplantation
Keywords: TTV
Biomarker
immunosuppression
precision medicine
kidney transplantation
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
Collaborators: name: BioMérieux
First posted: 2025-02-17
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, interventional, multicentric, open-label, parallel group, superiority randomized controlled trial.

Kidney transplant recipients from the 4 enrollment centers will be randomly assigned with a 1:1 allocation into experimental and control groups between 12- and 48-months post-transplantation, and prospectively followed for 36 months for the occurrence of a complication due to inadequate (over or under) immunosuppression.
Primary purpose: PREVENTION

Brief 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 criteria: 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 or vaccination within 3 months before 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

Primary outcomes:
measure: Compare the time from inclusion to first complication of inadequate immunosuppression between the experimental group, whose treatment is tailored on quarterly TTV viral load results, and the control group.
timeFrame: through study completion, an average of 6 years
Secondary outcomes:
measure: Proportion of patients with at least one complication of inadequate immunosuppression between the experimental and control groups at 36 months
timeFrame: through study completion, an average of 6 years
measure: Compare the rate of complications of inadequate immunosuppression between patients in the experimental and control groups.
timeFrame: through study completion, an average of 6 years
measure: Describe the nature and timing of various complications of inadequate immunosuppression in the experimental and control groups.
timeFrame: through study completion, an average of 6 years
measure: Compare the proportion of patients with adequate immunosuppressive therapy between the experimental and control groups.
timeFrame: through study completion, an average of 6 years
measure: Compare the proportion of quarterly systematic checks of TTV DNAemia in the target between patients in the experimental and control groups.
timeFrame: Every 3 months
measure: 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.
timeFrame: every 3 months
measure: Evaluate how nephrologists and biologists feel about using the new test in clinical practice.
timeFrame: 6th year
measure: Assess the cost-effectiveness of the intervention compared to standard care at 36 months from the French Health care System perspective
timeFrame: through study completion, an average of 6 years
Other outcomes:
Locations:
city: BORDEAUX (France)
country: France
facility: Service de Néphrologie-Transplantation-Dialyse I Hôpital Pellegrin I - CHU Bordeaux
city: Strasbourg (france)
country: France
facility: Service de Néphrologie, Dialyse et Transplantation Rénale Nouvel Hôpital Civil
city: TOULOUSE (France)
country: France
facility: Département de Néphrologie et Transplantation d'Organes Hôpital Rangueil - CHU de Toulouse
Study officials:
References: