Precision Medicine in LN: A Multicenter Proof-of-concept Study for Histopathological Biomarkers Analysis in Renal Biopsy

NCT05358652 | Unknown

• 1 other identifier: ISS 13844
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Lupus nephritis (LN) may affect approximately half of patients with Systemic Lupus Erythematosus (SLE). LN is a major cause of morbidity and the most important predictor of mortality in patients with SLE. Some 5-20% of patients with LN may develop end-stage renal disease within 10 years of follow-up from the time of diagnosis. Other studies have described progression to end-stage renal disease in 10-30% of patients with LN. The European League Against Rheumatism, the European Renal Association and the European Dialysis and Transplant Association have recently updated their recommendations for the management of LN. These recommend the use of intravenous (IV) methylprednisolone boluses followed by lower doses of oral glucocorticoids (GC) and place mycophenolate mofetil (MMF) and the European regimen of cyclophosphamide (CYC) as the immunosuppressive drugs of first choice, with the IV CYC regimen for certain more aggressive cases. They also consider the use of "multitarget therapy" based on the combination of tacrolimus (TAC) and MMF and GC in patients with proteinuria in the nephrotic range who have not responded to the first line of treatment. For refractory active renal disease, they recommend as an alternative the use of rituximab (RTX) 1000 mg IV repeated after 15 days. Belimumab has been shown to be significantly more effective than placebo in the treatment of patients with active LN. This finding will lead to positioning belimumab in the therapeutic algorithm for LN. However, in clinical practice these immunosuppressive drugs are not always effective in the treatment of LN, and even one in 3 patients with an initial favorable response may experience renal recurrence. The choice of the appropriate treatment for LN and its early initiation are key to improve the prognosis of these patients and to avoid progression to chronic renal failure. The identification of biomarkers capable of predicting the response (or lack thereof) to one or another therapy at the time of LN diagnosis would allow to implement precision medicine, thus constituting a revolution in the treatment of patients with LN. Allows more targeted treatments with greater specificity to be established. The objective of this project is to analyze histopathological biomarkers in the renal biopsy to predict the renal response to the different drugs used in the treatment of LN. This would contribute to a more specific and cost-effective therapeutic strategy.

Conditions

Lupus Nephritis; Systemic Lupus Erythematosus

Keywords

Lupus Nephritis; Systemic Lupus Erythematosus; Belimumab; Renal Biopsy

Outcome Measures

Primary Outcomes (1)

• complete renal response

  proteinuria \<0.5 g/24 hours and (near) normal estimated GFR

  5 years after renal biopsy

Secondary Outcomes (2)

• partial renal response

  5 years after renal biopsy

• proteinuria levels at 12 months of treatment,

  12 months after renal biopsy

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with a diagnosis of SLE according to the 1997 American College of Rheumatology (ACR) criteria.

You may qualify if:

• Patients with a diagnosis of SLE according to the 1997 American College of Rheumatology (ACR) criteria.
• Diagnosis of lupus nephritis type 3,4,5 or mixed forms of the above according to the International Society of Nephrology (ISN)/Renal Pathology Society (RPS) classification of LN.
• Date of performance of the renal biopsy: year 2000 or later. The reason for this time frame is the theoretical homogenization in the therapeutic management of LN with the introduction of MMF into the therapeutic armamentarium of LN and the extension of the use of the European intravenous cyclophosphamide guideline.
• Availability of the patient's first renal biopsy specimen preserved for re-evaluation.
• Availability of essential clinical data to carry out the study.
• Signature of the informed consent by the patient.

You may not qualify if:

• \- Refusal by the patient to sign the informed consent.

Sponsors & Collaborators

• Fundacin Biomedica Galicia Sur: lead
• Hospital Universitario 12 de Octubre: collaborator
• Germans Trias i Pujol Hospital: collaborator
• Hospital del Mar: collaborator
• Dr. Negrin University Hospital: collaborator
• Hospital Universitario Araba: collaborator

Study Sites (1)

IRIDIS-VIGO Group (Investigation in Rheumatology and Immune-Mediated Diseases), Instituto de Investigación Sanitaria Galicia Sur (IISGS).

Vigo, Pontevedra, 36213, Spain

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Renal biopsy

MeSH Terms

Conditions

Lupus Nephritis; Lupus Erythematosus, Systemic

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• José María Pego-Reigosa, Dr

  INSTITUTO DE INVESTIGACIÓN SANITARIA GALICIA SUR

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2022
• First Posted: May 3, 2022
• Study Start: October 15, 2021
• Primary Completion: July 15, 2022
• Study Completion: January 15, 2023
• Last Updated: May 3, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Since the beginning of the study
• Access Criteria: Being a participant in the study

Locations

ES (1)