- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica NCT07721857
Neutrophil Extracellular Traps and Lupus Nephritis
Dynamic Changes of Neutrophil Extracellular Traps in Lupus Nephritis and Their Role in Predicting Treatment Response.
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
In recent years, growing evidence has emphasized the role of innate immune dysregulation in the pathogenesis of lupus nephritis, particularly the involvement of neutrophils and aberrant cell death pathways. Among these mechanisms, neutrophil extracellular traps (NETs) have emerged as key mediators of autoimmune-driven inflammation. NETs are extracellular chromatin networks composed of DNA, histones, and granular proteins released by activated neutrophils during NETosis. Although originally described as antimicrobial defense structures, excessive NET formation and impaired degradation have been strongly implicated in systemic autoimmunity.
In lupus nephritis, NETs contribute to renal injury through multiple mechanisms, including exposure of nuclear autoantigens, amplification of type I interferon signaling, activation of complement pathways, and direct cytotoxic effects on endothelial cells and podocytes. Moreover, impaired NET clearance has been demonstrated in SLE, further promoting persistent immune activation and renal inflammation. Recent studies have also suggested that circulating NETs levels are elevated in patients with renal involvement and may correlate with disease activity and outcomes.
However, most available data are cross-sectional, and limited evidence exists regarding the dynamic changes of NETs in response to therapy. Therefore, evaluating NETs before and after treatment may provide important insights into their role as predictive and prognostic biomarkers and potential therapeutic targets in lupus nephritis.
Tipo di studio
Iscrizione (Stimato)
Contatti e Sedi
Contatto studio
- Nome: Salwa Salah elgendi, MD
- Numero di telefono: +0201005766155
- Email: salwaelgendi@aun.edu.eg
Backup dei contatti dello studio
- Nome: Mai Mostafa Mohamed, MD
- Numero di telefono: +0201223971678
- Email: mai_heamatology@aun.edu.eg
Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
- Adulto
Accetta volontari sani
Metodo di campionamento
Popolazione di studio
Descrizione
Inclusion criteria for LN group:
- Adult patients (≥ 18 and > 60 years) of either sex.
- Fulfill the 2019 EULAR/ACR Classification Criteria for Systemic Lupus Erythematosus (SLE) [11].
- Diagnosis of active lupus nephritis requiring a renal biopsy as per standard clinical indications (e.g., proteinuria ≥ 0.5 g/24h, active urinary sediment, unexplained rise in serum creatinine).
- Availability of an adequate renal biopsy specimen for histopathological evaluation according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2018 classification.
- Patients planned to initiate standard induction therapy (e.g., mycophenolate mofetil or cyclophosphamide with corticosteroids).
- Provision of written informed consent.
Inclusion Criteria for Control Groups:
1) SLE without nephritis: Patients meeting SLE criteria without any clinical or laboratory evidence of renal involvement (normal urinalysis, proteinuria < 0.3 g/24h, normal serum creatinine).
Exclusion Criteria:
Participants will be excluded if ANY of the following criteria apply:
Other Kidney Diseases:
- Presence of, or suspicion of, any other primary or significant secondary kidney disease unrelated to SLE (e.g., diabetic nephropathy, hypertensive nephrosclerosis, IgA nephropathy, significant drug-induced nephrotoxicity, rheumatoid arthritis, positive HBs antigen or HCV antibody).
Confounding Clinical Conditions:
- Presence of an active or recent major infection (e.g., sepsis, pneumonia, UTI) at the time of enrollment, as infection can significantly alter immune markers.
Presence of advanced chronic kidney disease (CKD Stage 4 or 5) predating the diagnosis of SLE.
3 · Pregnancy or lactation.
4. Recent use (within the last 3 months) of biologic therapies that may affect neutrophil function or NET formation.
5. Use of medications known to significantly alter neutrophil activity. 6. History of malignancy.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
Coorti e interventi
Gruppo / Coorte |
Intervento / Trattamento |
|---|---|
|
lupus nephritis group
Inclusion criteria for LN group:
|
Serum sample should be collected into a serum separator tube.
After clotting for 2 hours at room temperature or overnight at 4°C, and then centrifuging at 1000 × g for 20 minutes.
Assay freshly prepared serum immediately or store samples in aliquot at -20°C or -80°C for later use.
Avoid repeated freeze-thaw cycles.
|
|
control group
Inclusion Criteria for Control Groups: 1) SLE without nephritis: Patients meeting SLE criteria without any clinical or laboratory evidence of renal involvement (normal urinalysis, proteinuria < 0.3 g/24h, normal serum creatinine). |
Serum sample should be collected into a serum separator tube.
After clotting for 2 hours at room temperature or overnight at 4°C, and then centrifuging at 1000 × g for 20 minutes.
Assay freshly prepared serum immediately or store samples in aliquot at -20°C or -80°C for later use.
Avoid repeated freeze-thaw cycles.
|
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
The primary outcome of the study is the change in circulating neutrophil extracellular traps (NETs) levels, in patients with Lupus Nephritis
Lasso di tempo: 2 years
|
The primary outcome of the study is the change in circulating neutrophil extracellular traps (NETs) levels, in patients with Lupus Nephritis.
NETs levels will be assessed at baseline (prior to initiation of therapy), and at 6 months following treatment
|
2 years
|
Collaboratori e investigatori
Sponsor
Pubblicazioni e link utili
Pubblicazioni generali
- Mok CC, Teng YKO, Saxena R, Tanaka Y. Treatment of lupus nephritis: consensus, evidence and perspectives. Nat Rev Rheumatol. 2023 Apr;19(4):227-238. doi: 10.1038/s41584-023-00925-5. Epub 2023 Mar 2.
- Chen X, Gao D, Wang M, Wang L, Hu H, Wen C, Tang Y. Neutrophil Extracellular Traps in Systemic Lupus Erythematosus: Pathogenic Mechanisms, Crosstalk with Oxidative Stress, and Antioxidant Therapeutic Potential. Antioxidants (Basel). 2025 Dec 23;15(1):25. doi: 10.3390/antiox15010025.
- Yu Y, Su K. Neutrophil Extracellular Traps and Systemic Lupus Erythematosus. J Clin Cell Immunol. 2013 Apr;4:139. doi: 10.4172/2155-9899.1000139.
- Carmona-Rivera C, Zhao W, Yalavarthi S, Kaplan MJ. Neutrophil extracellular traps induce endothelial dysfunction in systemic lupus erythematosus through the activation of matrix metalloproteinase-2. Ann Rheum Dis. 2015 Jul;74(7):1417-24. doi: 10.1136/annrheumdis-2013-204837. Epub 2014 Feb 25.
- Hakkim A, Furnrohr BG, Amann K, Laube B, Abed UA, Brinkmann V, Herrmann M, Voll RE, Zychlinsky A. Impairment of neutrophil extracellular trap degradation is associated with lupus nephritis. Proc Natl Acad Sci U S A. 2010 May 25;107(21):9813-8. doi: 10.1073/pnas.0909927107. Epub 2010 May 3.
- Liu L, de Leeuw K, van Goor H, Doornbos-van der Meer B, Arends S, Westra J. Neutrophil extracellular traps and oxidative stress in systemic lupus erythematosus patients with and without renal involvement. Arthritis Res Ther. 2024 Dec 19;26(1):220. doi: 10.1186/s13075-024-03454-y.
- Gupta S, Kaplan MJ. The role of neutrophils and NETosis in autoimmune and renal diseases. Nat Rev Nephrol. 2016 Jul;12(7):402-13. doi: 10.1038/nrneph.2016.71. Epub 2016 May 31.
- Lichtnekert J, Anders HJ. Lupus nephritis-related chronic kidney disease. Nat Rev Rheumatol. 2024 Nov;20(11):699-711. doi: 10.1038/s41584-024-01158-w. Epub 2024 Sep 24.
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Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
- Malattie urogenitali
- Malattie urogenitali maschili
- Malattie renali
- Malattie urologiche
- Malattie urogenitali femminili
- Malattie urogenitali femminili e complicanze della gravidanza
- Malattie del tessuto connettivo
- Malattie autoimmuni
- Malattie del sistema immunitario
- Glomerulonefrite
- Lupus Eritematoso, Sistemico
- Nefrite
- Malattie della pelle e del tessuto connettivo
- Nefrite da lupus
Altri numeri di identificazione dello studio
- DCNETLN
Piano per i dati dei singoli partecipanti (IPD)
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Informazioni su farmaci e dispositivi, documenti di studio
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