Urinary T Cell Biomarker for Prediction in ANCA Glomerulonephritis

Glomerulonephritis Acute Clinical Trial

Official title:

Phenotype of Urinary CD4+ T Cells as Biomarkers for Prediction of Outcome in ANCA Glomerulonephritis

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04320667
• Other study ID #: ANCAFLURINOCYTE
• Status: Active, not recruiting
• Start date: November 19, 2019
• Est. completion date: December 2022

Study information

• Verified date: July 2022
• Source: Charite University, Berlin, Germany
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Urinary T lymphocytes may be predictive for clinical outcome in patients with ANCA associated glomerulonephritis (ANCA GN). The investigators hypothesize that the amount of CD4+ effector/memory T cells in urine at time of diagnosis predicts the outcome of patients with active ANCA GN after 6 months of therapy. In a prospective, six-months follow-up study patients' urine will be analysed by flow cytometry every 60 days (+/- 10d). Treatment will be performed to the discretion of the treating clinician. After 6 months of treatment response will be determined as either complete response or partial response.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 79
• Est. completion date: December 2022
• Est. primary completion date: September 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Informed consent

• Biopsy proven ANCA related glomerulonephritis

• In absence of biopsy clinical diagnosis of ANCA related glomerulonephritis

Exclusion Criteria:

• Biopsy proven non-ANCA related kidney disease

• Active menstrual bleeding

• Urinary tract infection

• Kidney transplantation during observational period

Related Conditions & MeSH terms

• Glomerulonephritis
• Glomerulonephritis Acute

Intervention

Diagnostic Test:
• Flow cytometry analysis of urine samples
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

Locations

Country	Name	City	State
Germany	Charité - Universitätsmedizin Berlin	Berlin	Deutschland
United Kingdom	The Royal Free London	London

Sponsors (2)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany	Berlin Institute of Health

Countries where clinical trial is conducted

Germany,  United Kingdom, 

References & Publications (4)

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. — View Citation

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. — View Citation

Lieberthal JG, Cuthbertson D, Carette S, Hoffman GS, Khalidi NA, Koening CL, Langford CA, Maksimowicz-McKinnon K, Seo P, Specks U, Ytterberg SR, Merkel PA, Monach PA; Vasculitis Clinical Research Consortium. urinary biomarkers in relapsing antineutrophil cytoplasmic antibody-associated vasculitis. J Rheumatol. 2013 May;40(5):674-83. doi: 10.3899/jrheum.120879. Epub 2013 Apr 1. — View Citation

Tomasson G, Grayson PC, Mahr AD, Lavalley M, Merkel PA. Value of ANCA measurements during remission to predict a relapse of ANCA-associated vasculitis--a meta-analysis. Rheumatology (Oxford). 2012 Jan;51(1):100-9. doi: 10.1093/rheumatology/ker280. Epub 2011 Oct 29. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phenotype of CD4+ T cells at time point 0 predictive of clinical outcome in patients with active ANCA-assosciated glomerulonephritis	Urinary CD4+ effector/memory T cell counts at time point 0 (time of diagnosis) predict clinical outcome (complete or partial response) after 6 months of treatment in patients with active ANCA-assosciated glomerulonephritis. The frequency of effector/memory CD4+ T lymphocytes is higher in patients with non- or partial response.; Complete response at 24 weeks: BVAS = 0 Partial response at 24 weeks: at least one renal element of the BVAS score.	6 months
Secondary	Analysis of patients with persistent renal abnormalities as partial response		6 months
Secondary	Phenotype of CD8+ T cells at time point 0 predictive of clinical outcome in patients with active ANCA-assosciated glomerulonephritis	Urinary CD8+ effector/memory T cell counts at time point 0 (time of diagnosis) predict clinical outcome (complete or partial response) after 6 months of treatment in patients with active ANCA-assosciated glomerulonephritis. The frequency of effector/memory CD8+ T lymphocytes is higher in patients with non- or partial response.	6 months
Secondary	Subgroup analysis according to treatment		6 months
Secondary	Diagnosis of active glomerulonephritis in Patients with ANCA associated vasculitis	Diagnosis according to initial T cell count	6 months
Secondary	Prediction of complete or partial response according to normalization of the amount of urinary T cells at time point 2 and 4		6 months