PRE-FLARED: Urinary T Lymphocytes Predict Renal Flares in Patients With Inactive ANCA-associated Glomerulonephritis

• Sponsor: Charite University, Berlin, Germany (Other)
• Overall Status: Completed
• CT.gov ID: NCT04428398
• Collaborator: (none)
• Enrollment: 100
• Locations: 2
• Actual Duration (Months): 16
• Patients Per Site: 50
• Patients Per Site Per Month: 3.1

Study Details

Study Description

Brief Summary

Urinary CD4+ and CD8+ T lymphocytes may predict renal flares in patients with inactive ANCA-associated vasculitis and thus serve as early non-invasive biomarkers. Urine samples of patients with inactive renal ANCA-vasculitis will be analysed by flow cytometry and compared to clinical outcome after 6 months.

Condition or Disease	Intervention/Treatment	Phase
Glomerulonephritis Acute	Diagnostic Test: Analysis of urine samples with flow cytometry

Detailed Description

Data of previous studies have shown that counts of urinary T lymphocyte subsets correlate with disease activity in several immunological renal diseases, e.g. ANCA-associated glomerulonephritis. Thus, study authors hypothesise that CD4+, respectively CD8+, T effector memory lymphocytes found in urine samples of patients with inactive ANCA-vasculitis predict subsequent renal flares. Therefore, quantification of these cellular subsets might reliably predict relapse of ANCA associated glomerulonephritis at an early stage. In a prospective experimental study urine of patients with ANCA-vasculitis and no renal involvement or patients in renal remission will be analysed by flow cytometry. After 6 months of observation, clinical outcome and potential renal relapse will be determined and correlated to initial T lymphocyte count.

Study Design

• Study Type: Observational
• Actual Enrollment: 100 participants
• Observational Model: Case-Only
• Time Perspective: Prospective
• Official Title: Urinary T Lymphocytes Predict Renal Flares in Patients With Inactive Anti-neutrophil Cytoplasmic Antibody (ANCA) Associated Glomerulonephritis
• Actual Study Start Date: May 1, 2020
• Actual Primary Completion Date: Sep 1, 2021
• Actual Study Completion Date: Sep 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
No renal involvement Patients with ANCA-vasculitis and no ANCA-associated renal involvement in disease history	Diagnostic Test: Analysis of urine samples with flow cytometry; Urine samples will be conserved and frozen upon arrival. All samples will be stained according to T cell and TEC (tubular epithelial cells) panel with fluorochromes. T cell panel: CD3, CD4, CD8, CCR7, CD45RO, CD28, CD279; TEC panel: vimentin, cytokeratine, CD10, CD13, CD227, CD326
Renal remission Patient with ANCA-vasculitis in renal remission	Diagnostic Test: Analysis of urine samples with flow cytometry; Urine samples will be conserved and frozen upon arrival. All samples will be stained according to T cell and TEC (tubular epithelial cells) panel with fluorochromes. T cell panel: CD3, CD4, CD8, CCR7, CD45RO, CD28, CD279; TEC panel: vimentin, cytokeratine, CD10, CD13, CD227, CD326

Outcome Measures

Primary Outcome Measures

1. Prediction of renal relapse after six months depending initial CD4+ count [6 months]

   relapse defined as Birmingham Vasculitis Activity Score (BVAS) > 1 + at least one renal element or intensified treatment regime (Prednisolon equivalent > 20 mg/d or novel induction treatment with Rituximab or Cyclophosphamide)

Secondary Outcome Measures

1. Prediction of renal relapse after six months depending initial CD8+ count [6 months]

2. Prediction of renal relapse after six months depending initial CD4+/CD8+ subsets [6 months]

   Subsets: T effector memory cells (CD45RO+/CCR7-)

3. Prediction of renal relapse after 12 months depending initial CD4+ count [12 months]

4. Prediction of renal relapse after 12 months depending initial CD8+ count [12 months]

5. Prediction of renal relapse after 12 months depending initial CD4+/CD8+ subsets [12 months]

   Subsets: T effector memory cells (CD45RO+/CCR7-)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• diagnosed ANCA-associated vasculitis (clinical diagnosis of granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis or microscopic polyangiitis consistent with the Chapel-Hill consensus definitions AND positive test for proteinase 3-ANCA or myeloperoxidase-ANCA)

• no currently active renal involvement (defined as BVAS = 0 with exception of hematuria or proteinuria as signs of renal scars)

• written and informed consent

Exclusion Criteria:

• urinary tract infection

• active menstrual bleeding

• current therapy with rituximab

• active renal involvement

• other active renal disease (e.g. diabetic nephropathy)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Charité - Universitätsmedizin Berlin	Berlin		Germany	10117
2	Helios Klinikum Berlin-Buch	Berlin		Germany	13125

Sponsors and Collaborators

• Charite University, Berlin, Germany

Investigators

• Principal Investigator: Philipp Enghard, Charite University, Berlin, Germany
• Principal Investigator: Adrian Schreiber, PD Dr. med., Charite University, Berlin, Germany

Study Documents (Full-Text)

None provided.

More Information

Publications

• Abdulahad WH, Kallenberg CG, Limburg PC, Stegeman CA. Urinary CD4+ effector memory T cells reflect renal disease activity in antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2009 Sep;60(9):2830-8. doi: 10.1002/art.24747.
• Córdova-Sánchez BM, Mejía-Vilet JM, Morales-Buenrostro LE, Loyola-Rodríguez G, Uribe-Uribe NO, Correa-Rotter R. Clinical presentation and outcome prediction of clinical, serological, and histopathological classification schemes in ANCA-associated vasculitis with renal involvement. Clin Rheumatol. 2016 Jul;35(7):1805-16. doi: 10.1007/s10067-016-3195-z. Epub 2016 Feb 6.
• Enghard P, Rieder C, Kopetschke K, Klocke JR, Undeutsch R, Biesen R, Dragun D, Gollasch M, Schneider U, Aupperle K, Humrich JY, Hiepe F, Backhaus M, Radbruch AH, Burmester GR, Riemekasten G. Urinary CD4 T cells identify SLE patients with proliferative lupus nephritis and can be used to monitor treatment response. Ann Rheum Dis. 2014 Jan;73(1):277-83. doi: 10.1136/annrheumdis-2012-202784. Epub 2013 Mar 8.
• Göçeroğlu A, Berden AE, Fiocco M, Floßmann O, Westman KW, Ferrario F, Gaskin G, Pusey CD, Hagen EC, Noël LH, Rasmussen N, Waldherr R, Walsh M, Bruijn JA, Jayne DR, Bajema IM; European Vasculitis Society (EUVAS). ANCA-Associated Glomerulonephritis: Risk Factors for Renal Relapse. PLoS One. 2016 Dec 14;11(12):e0165402. doi: 10.1371/journal.pone.0165402. eCollection 2016.
• Menez S, Hruskova Z, Scott J, Cormican S, Chen M, Salama AD, Alasfar S, Little MA, Safrankova H, Honsova E, Tesar V, Geetha D. Predictors of Renal Outcomes in Sclerotic Class Anti-Neutrophil Cytoplasmic Antibody Glomerulonephritis. Am J Nephrol. 2018;48(6):465-471. doi: 10.1159/000494840. Epub 2018 Nov 23.

• Responsible Party: Philipp Enghard, PD Dr. med., Charite University, Berlin, Germany
• ClinicalTrials.gov Identifier: NCT04428398
• Other Study ID Numbers: PRE-FLARED
• First Posted: Jun 11, 2020
• Last Update Posted: Mar 9, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Philipp Enghard, PD Dr. med., Charite University, Berlin, Germany: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Pauci-Immune Glomerulonephritis; urinary biomarker; Churg-Strauss Syndrome; Microscopic Polyangiitis; Granulomatosis with Polyangiitis; effector memory T lymphocytes; prediction
• Additional relevant MeSH terms: Glomerulonephritis

Study Results

No Results Posted as of Mar 9, 2022