Treatment of Early Borderline Lesions in Low Immunological Risk Kidney Transplant Patients (TRAINING)

November 29, 2023 updated by: Fundación Canaria de Investigación Sanitaria

Treatment of Early Borderline Lesions in Low Immunological Risk Kidney Transplant Patients: a Spanish Multicenter, Randomized, Controlled Parallel-group Trial: The TRAINING Study

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

80

Phase

  • Phase 4

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

  • Spain
      • Barcelona, Spain, 08025
        • Recruiting
        • Fundacion Puigvert
        • Contact:
          • Luis Guirado, MD, PhD
      • Barcelona, Spain, 08035
        • Recruiting
        • Hospital Universitari Valld´Hebron
        • Contact:
          • Manel Perello, MD
      • Malaga, Spain, 29010
        • Recruiting
        • Veronica Lopez Jimenez
        • Contact:
    • None Selected
      • Tenerife, None Selected, Spain, 38320

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 >2.5 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.
  • CMV 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.

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: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental
Normal treatment (Steroids, tacrolimus and mycophenolate) 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. Then continue with the normal treatment: Steroids (5 mg/day), tacrolimus (0.1 mg/kg/day) and mycophenolate (1000 mg/day).
Active Comparator: Normal treatment
Normal treatment (Steroids, tacrolimus and mycophenolate) arm
Drug: Normal Treatment
When Borderline lesions are present in protocol biopsy, administer the normal treatment: Steroids (5 mg/day), tacrolimus (0.1 mg/kg/day) and mycophenolate (1000 mg/day)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
24 months
Renal function measured with CKD-EPI
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
24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Graft Survival
Time Frame: 24 months
Graft survival after kidney transplant in both groups
24 months
Patient Survival
Time Frame: 24 months
Patient survival after kidney transplant in both groups
24 months
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
24 months
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
24 months
Assess the Adherence to Immunosuppressive Therapy in the Two Treatment Groups
Time Frame: 24 months
The Basle scale was used to assess adherence to immunosuppressive therapy.
24 months
Blood Pressure mmHg
Time Frame: 24 months
Blood pressure after kidney transplant in both groups at 24 months
24 months
Lipid Profile cholesterol, triglycerides
Time Frame: 24 months
Lipid profile after kidney transplant in both groups at 24 months
24 months
Klotho levels pg/ml
Time Frame: 24 months
Klotho levels after kidney transplant in both groups at 1, 3, 6, 12 and 24 months
24 months

Collaborators and Investigators

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

Sponsor

Fundación Canaria de Investigación Sanitaria

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)

July 5, 2022

Primary Completion (Estimated)

June 1, 2024

Study Completion (Estimated)

June 30, 2024

Study Registration Dates

First Submitted

June 18, 2021

First Submitted That Met QC Criteria

June 18, 2021

First Posted (Actual)

June 23, 2021

Study Record Updates

Last Update Posted (Estimated)

December 5, 2023

Last Update Submitted That Met QC Criteria

November 29, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TRAINING

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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