Urinary T Cell Biomarker for Prediction in ANCA Glomerulonephritis

NCT04320667 | Unknown

• 1 other identifier: ANCAFLURINOCYTE
• Study Type: observational
• Target: 79
• Locations: 2 countries
• Sites: 2

Brief 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.

Conditions

Glomerulonephritis Acute

Keywords

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Pauci-Immune Vasculitis; Churg-Strauss Syndrome; Granulomatosis with Polyangiitis; Microscopic Polyangiitis; urinary biomarker; outcome; prediction,; urinary effector memory T lymphocytes; glomerulonephritis; non-invasive biomarker; flow cytometry; treatment outcome; CD4-Positive T-Lymphocytes/immunology

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Analysis of patients with persistent renal abnormalities as partial response

  6 months

• Phenotype of CD8+ T cells at time point 0 predictive of clinical outcome in patients with active ANCA-assosciated glomerulonephritis

  6 months

• Subgroup analysis according to treatment

  6 months

• Diagnosis of active glomerulonephritis in Patients with ANCA associated vasculitis

  6 months

• Prediction of complete or partial response according to normalization of the amount of urinary T cells at time point 2 and 4

  6 months

Study Arms (2)

Active ANCA glomerulonephritis

Patients with ANCA related disease (Microscopic Polyangiitis, Granulomatosis with Polyangiitis or Churg-Strauss Syndrome) and active renal involvement

Diagnostic Test: Flow cytometry analysis of urine samples

Control

Patients with ANCA related disease (MPA, GPA, CSS) without renal involvement or complete remission

Diagnostic Test: Flow cytometry analysis of urine samples

Interventions

Flow cytometry analysis of urine samples DIAGNOSTIC_TEST

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

Active ANCA glomerulonephritis; Control

Eligibility Criteria

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

Study Population

Patients at medical wards of Charité Universitätsmedizin Berlin and University College London, The Royal Free Hospital

You may qualify if:

• Informed consent
• Biopsy proven ANCA related glomerulonephritis
• In absence of biopsy clinical diagnosis of ANCA related glomerulonephritis

You may not qualify if:

• Biopsy proven non-ANCA related kidney disease
• Active menstrual bleeding
• Urinary tract infection
• Kidney transplantation during observational period

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead
• Berlin Institute of Health: collaborator

Study Sites (2)

Charité - Universitätsmedizin Berlin

Berlin, Deutschland, 10117, Germany

Location

The Royal Free London

London, NW3 2QG, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 23475982 BACKGROUND

• 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.

  PMID: 19714581 BACKGROUND

• 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.

  PMID: 23547217 BACKGROUND

• 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.

  PMID: 22039267 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

urine, lymphocytes

MeSH Terms

Conditions

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Churg-Strauss Syndrome; Granulomatosis with Polyangiitis; Microscopic Polyangiitis; Glomerulonephritis

Condition Hierarchy (Ancestors)

Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Granuloma; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Philipp Enghard, PD Dr. med.

  Charite University, Berlin, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PD Dr. med.

Study Record Dates

• First Submitted: March 23, 2020
• First Posted: March 25, 2020
• Study Start: November 19, 2019
• Primary Completion: September 1, 2021
• Study Completion: December 1, 2022
• Last Updated: July 29, 2022

Record last verified: 2022-07

Locations

DE (1); GB (1)