TTV-based mAnagement Of Long-term ImmunosuppreSsion in Kidney Transplantation

NCT06829719 | Recruiting

• 1 other identifier: 69HCL23_0834
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 4

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.

Conditions

Infection; Cancer; Rejection; Kidney Transplantation

Keywords

TTV; Biomarker; immunosuppression; precision medicine; kidney transplantation

Outcome Measures

Primary Outcomes (1)

• 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.

  Time from inclusion 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 Outcomes (8)

• Proportion of patients with at least one complication of inadequate immunosuppression between the experimental and control groups at 36 months

  through study completion, an average of 6 years

• Compare the rate of complications of inadequate immunosuppression between patients in the experimental and control groups.

  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.

  through study completion, an average of 6 years

• Compare the proportion of patients with adequate immunosuppressive therapy between the experimental and control groups.

  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.

  Every 3 months

Study Arms (2)

TTV-guided immunosuppression

EXPERIMENTAL

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).

Biological: TTV DNAemia; Other: EQ-5D-5L questionnaire; Biological: Biological tests

Standard Immunosuppression

OTHER

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.

Biological: TTV DNAemia; Other: EQ-5D-5L questionnaire; Biological: Biological tests

Interventions

TTV DNAemia BIOLOGICAL

Every 3 months, one sample added at the same time (7mL) of a routine laboratory analysis for TTV DNAemia

Standard Immunosuppression; TTV-guided immunosuppression

EQ-5D-5L questionnaire OTHER

Completed every 6 months and each time a complication of interest occurs

Standard Immunosuppression; TTV-guided immunosuppression

Biological tests BIOLOGICAL

Biological tests as routine care procedure (creatinine, CNI pre-dose trough level) will be performed every 6 months

Standard Immunosuppression; TTV-guided immunosuppression

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult ≥ 18 years-old
• Recipient of a kidney allograft (third graft at most)
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Hospices Civils de Lyon: lead
• BioMérieux: collaborator

Study Sites (4)

Service de Néphrologie-Transplantation-Dialyse I Hôpital Pellegrin I - CHU Bordeaux

Bordeaux (France), 33000, France

NOT YET RECRUITING

Service de transplantation, néphrologie et immunologie clinique Hospices Civils de Lyon, Hôpital Edouard Herriot

Lyon, 69003, France

RECRUITING

Service de Néphrologie, Dialyse et Transplantation Rénale Nouvel Hôpital Civil

Strasbourg (france), 67091, France

NOT YET RECRUITING

Département de Néphrologie et Transplantation d'Organes Hôpital Rangueil - CHU de Toulouse

Toulouse (France), 31059, France

NOT YET RECRUITING

MeSH Terms

Conditions

Infections; Neoplasms; Rejection, Psychology

Condition Hierarchy (Ancestors)

Social Behavior; Behavior

Central Study Contacts

Olivier THAUNAT, Professor MD, PhD

CONTACT

+334.72.11.69.28; olivier.thaunat@chu-lyon.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: TTV DNAemia will be measured every 3 months for all patients but the results will not be communicated to the physicians for patients from the control group.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: February 3, 2025
• First Posted: February 17, 2025
• Study Start: April 23, 2025
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): February 2, 2031
• Last Updated: July 2, 2025

Record last verified: 2025-02

Locations

FR (4)