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

Официальное название

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

Обзор

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.

Вмешательства

• Биопрепарат TTV DNAemia
  Every 6 months, one sample added at the same time (7mL) of a routine laboratory analysis for TTV DNAemia
• Другое EQ-5D-5L questionnaire
  Completed every 6 months and each time a complication of interest occurs
• Биопрепарат Biological tests
  Biological tests as routine care procedure (creatinine, CNI pre-dose trough level) will be performed every 6 months

Первичные конечные точки

• 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. [Срок оценки: through study completion, an average of 6 years]

Вторичные конечные точки (8)

• Proportion of patients with at least one complication of inadequate immunosuppression between the experimental and control groups at 36 months [Срок оценки: through study completion, an average of 6 years]
• Compare the rate of complications of inadequate immunosuppression between patients in the experimental and control groups. [Срок оценки: 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. [Срок оценки: through study completion, an average of 6 years]
• Compare the proportion of patients with adequate immunosuppressive therapy between the experimental and control groups. [Срок оценки: 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. [Срок оценки: 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. [Срок оценки: every 6 months]
• Evaluate how nephrologists and biologists feel about using the new test in clinical practice. [Срок оценки: 6th year]
• Assess the cost-effectiveness of the intervention compared to standard care at 36 months from the French Health care System perspective [Срок оценки: through study completion, an average of 6 years]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Профилактика

Центры проведения

Франция · 4 центра

• Service de Néphrologie-Transplantation-Dialyse I Hôpital Pellegrin I - CHU Bordeaux — Bordeaux (France)
• Service de transplantation, néphrologie et immunologie clinique Hospices Civils de Lyon, H — Lyon
• Service de Néphrologie, Dialyse et Transplantation Rénale Nouvel Hôpital Civil — Strasbourg (france)
• Département de Néphrologie et Transplantation d'Organes Hôpital Rangueil - CHU de Toulouse — Toulouse (France)

Публикации

• Doberer K, Kapps S, Haupenthal F, Bond G. Immune Monitoring Goes Viral - Torque Teno Virus for Immunologic Risk Stratification After Kidney Transplantation. Transpl Int. 2025 Nov 14;38:15074. doi: 10.3389/ti.2025.15074. eCollection 2025. PMID 41323957

Идентификаторы

NCT: NCT06829719 · 69HCL23_0834

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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