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Trial record 1 of 1 for:    NCT04936282
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Treatment of Early Borderline Lesions in Low Immunological Risk Kidney Transplant Patients (TRAINING)

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ClinicalTrials.gov Identifier: NCT04936282
Recruitment Status : Not yet recruiting
First Posted : June 23, 2021
Last Update Posted : June 23, 2021
Information provided by (Responsible Party):
Fundación Canaria de Investigación Sanitaria

Brief Summary:

Background: Subclinical inflammation, including borderline lesions (BL), is very common (30-40%) after kidney transplantation (KT), even in low immunological risk patients, and can lead to interstitial fibrosis/tubular atrophy (IFTA) and worsening of renal function with graft loss. Few controlled studies have analyzed the therapeutic benefit of these BL on renal function and graft histology. Furthermore, these studies have only used bolus steroids, which may be insufficient to slow the progression of these lesions. Klotho, a transmembrane protein produced mainly in the kidney with antifibrotic properties, plays a crucial role in the senescence-inflammation binomial of kidney tissue. Systemic and local inflammation decrease renal tissue expression and soluble levels of α-klotho. It is therefore important to determine whether treatment of BL prevents a decrease in α klotho levels, progression of IFTA, and loss of kidney function.

Methods: The TRAINING study will randomize 80 patients with low immunological risk who will receive their first KT. The aim of the study is to determine whether the treatment of early BL (3rd month post-KT) with polyclonal rabbit antithymocyte globulin (Grafalon®) (6 mg/kg/day) prevents or decreases the progression of IFTA and the worsening of graft function compared to conventional therapy after two years post-TX, as well as to analyze whether treatment of BL with Grafalon® can modify the expression and levels of klotho, as well as the pro-inflammatory cytokines that regulate its expression.

Condition or disease Intervention/treatment Phase
Kidney Transplant Failure and Rejection Drug: Grafalon Drug: Normal Treatment: Steroids, tacrolimus and mycophenolate Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Treatment of Early Borderline Lesions in Low Immunological Risk Kidney Transplant Patients: a Spanish Multicenter, Randomized, Controlled Parallel-group Trial: The TRAINING Study
Estimated Study Start Date : January 2022
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : December 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Tacrolimus

Arm Intervention/treatment
Experimental: Steroids, tacrolimus, mycophenolate and Grafalon
Normal treatment for first 90 days, then add Grafalon single-dose if borderline lesions are present in protocol biopsy (performed at third month post-transplantation)
Drug: Grafalon
When Borderline lesions are present in protocol biopsy, administer Grafalon ® 6 mg/kg/day in a single day.

Active Comparator: Steroids, tacrolimus and mycophenolate
Normal treatment arm
Drug: Normal Treatment: Steroids, tacrolimus and mycophenolate
When Borderline lesions are present in protocol biopsy, administer treatment according to routine clinical practice

Primary Outcome Measures :
  1. Presence of interstitial fibrosis/tubular atrophy (IFTA) [ Time Frame: 24 months ]
    Measurement at 24 months according to the Banff classification. The Banff Classification of Allograft Pathology is an international consensus classification for the reporting of biopsies from solid organ transplant.

  2. Renal function [ Time Frame: 24 months ]
    Renal function after kidney transplant in both groups at 24 months measured according to glomerular filtration rate determined by CKD-EPI formula

Secondary Outcome Measures :
  1. Graft Survival [ Time Frame: 24 months ]
    Graft survival after kidney transplant in both groups

  2. Patient Survival [ Time Frame: 24 months ]
    Patient survival after kidney transplant in both groups

  3. Assess the Adherence to Immunosuppressive Therapy in the Two Treatment Groups [ Time Frame: 24 months ]
    The Basle scale was used to assess adherence (BAASIS questionnaire) to immunosuppressive therapy.

  4. Incidence of Diabetes Mellitus [ Time Frame: 24 months ]
    Incidence of diabetes mellitus after kidney transplant in both groups at 1, 2, 3, 4, 6, 9, 12, 18 and 24 months

  5. Blood Pressure [ Time Frame: 24 months ]
    Blood pressure after kidney transplant in both groups at 24 months

  6. Number of Participants With Acute Rejection Lesions [ Time Frame: 24 months ]
    Patients with acute rejection lesions (including subclinical rejection) at 24 months according to Banff classification

  7. Lipid Profile [ Time Frame: 24 months ]
    Lipid profile after kidney transplant in both groups at 24 months

  8. Klotho levels [ Time Frame: 24 months ]
    Klotho levels after kidney transplant in both groups at 1, 3, 6, 12 and 24 months

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients of either sex, older than 18 years, with no immunological risk (PRA<20% and absence of DSA), who receive their first deceased donor or living donor KT.
  • Presence of BL, excluding isolated inflammation (t0, i>0) and isolated tubulitis (t>0, i0).
  • Patients receiving tacrolimus in combination with mycophenolic acid (MPA) and steroids.
  • Absence of clinical or subclinical and histological immunological dysfunction before randomization.
  • Absence of de novo DSA anti-HLA antibodies at the time of randomization.
  • Provision of written informed consent.
  • Acceptance of efficient contraception in women.

Exclusion Criteria:

  • Recipients of a multi-organ transplant.
  • Re-transplants.
  • Patients without inflammation in the third month protocol biopsy (i0,t0), or with isolated inflammation without tubulitis (t0,i>0) or isolated tubulitis without inflammation (t>0,i0).
  • Presence of DSA antibodies before transplantation or at randomization.
  • Cold ischemia time >30 hours.
  • Serum creatinine >2 mg/dl or proteinuria >1 g/day at randomization.
  • Presence of significant thrombopenia (<100,000/mm3) or leukopenia (<3000 mm/3) at randomization.
  • Previous episode of clinical or subclinical rejection (≥IA) before randomization.
  • Presence of BL before randomization.
  • CMV infection or disease in the first three months after transplantation.
  • BK-polyomavirus nephropathy at randomization.
  • Recurrent or de novo glomerulonephritis.
  • Treatment with immunosuppressive drugs other than those in this clinical trial.
  • Patients who are positive for the human immunodeficiency virus (HIV) or with severe systemic infection, who, in the opinion of the investigator, require continued therapy.
  • Previous (within the last 5 years) or present malignancy, except excised basal or squamous cell carcinoma.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04936282

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Contact: Pedro Ruiz-Esteban, PhD +34951291542 pedro_ruiz_esteban@hotmail.com

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Hospital Universitario de Canarias
Tenerife, None Selected, Spain, 38320
Contact: Armando Torres, MD,PhD       atorresram@gmail.com   
Fundación Puigvert
Barcelona, Spain, 08025
Contact: Luis Guirado, MD, PhD         
Hospital Universitari Valld´Hebron
Barcelona, Spain, 08035
Contact: Manel Perello, MD         
Hospital Regional Universitario de Málaga
Malaga, Spain, 29010
Contact: Domingo Hernández, MD, PhD         
Sponsors and Collaborators
Fundación Canaria de Investigación Sanitaria

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Fundación Canaria de Investigación Sanitaria
ClinicalTrials.gov Identifier: NCT04936282    
Other Study ID Numbers: TRAINING
First Posted: June 23, 2021    Key Record Dates
Last Update Posted: June 23, 2021
Last Verified: June 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Fundación Canaria de Investigación Sanitaria:
borderline lesions
low immunological risk
subclinical inflammation
kidney transplant
Additional relevant MeSH terms:
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Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action