Urinary T Cell Biomarker for Prediction in Lupus Nephritis

Lupus Nephritis Clinical Trial

Official title:

Phenotype of Urinary CD4+ T Cells as Biomarkers for Prediction of Outcome in Lupus Nephritis

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04320797
• Other study ID #: SLEFLURINOCYTE
• Status: Active, not recruiting
• Start date: July 30, 2019
• Est. completion date: September 2022

Study information

• Verified date: March 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 lupus nephritis. 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 lupus nephritis (LN) 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: September 2022
• Est. primary completion date: September 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Biopsy proven lupus nephritis

• In absence of a biopsy a SLEDAI of at least 10 & at least two renal elements of the renal SLEDAI (rSLEDAI)

• Informed consent

• Diagnosis of SLE according to the American College of Rheumatology (ACR) criteria

Exclusion Criteria:

• Biopsy-proven non-SLE related disease

• Urinary tract infection

• Active menstrual bleeding

• Kidney transplantation during observation time

Related Conditions & MeSH terms

• Lupus Nephritis
• Nephritis

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
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)

Arazi A, Rao DA, Berthier CC, Davidson A, Liu Y, Hoover PJ, Chicoine A, Eisenhaure TM, Jonsson AH, Li S, Lieb DJ, Zhang F, Slowikowski K, Browne EP, Noma A, Sutherby D, Steelman S, Smilek DE, Tosta P, Apruzzese W, Massarotti E, Dall'Era M, Park M, Kamen DL, Furie RA, Payan-Schober F, Pendergraft WF 3rd, McInnis EA, Buyon JP, Petri MA, Putterman C, Kalunian KC, Woodle ES, Lederer JA, Hildeman DA, Nusbaum C, Raychaudhuri S, Kretzler M, Anolik JH, Brenner MB, Wofsy D, Hacohen N, Diamond B; Accelerating Medicines Partnership in SLE network. The immune cell landscape in kidneys of patients with lupus nephritis. Nat Immunol. 2019 Jul;20(7):902-914. doi: 10.1038/s41590-019-0398-x. Epub 2019 Jun 17. Erratum in: Nat Immunol. 2019 Aug 13;:. — View Citation

Dolff S, Abdulahad WH, Arends S, van Dijk MC, Limburg PC, Kallenberg CG, Bijl M. Urinary CD8+ T-cell counts discriminate between active and inactive lupus nephritis. Arthritis Res Ther. 2013 Feb 27;15(1):R36. doi: 10.1186/ar4189. — 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

Kopetschke K, Klocke J, Grießbach AS, Humrich JY, Biesen R, Dragun D, Burmester GR, Enghard P, Riemekasten G. The cellular signature of urinary immune cells in Lupus nephritis: new insights into potential biomarkers. Arthritis Res Ther. 2015 Apr 3;17:94. doi: 10.1186/s13075-015-0600-y. — 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 lupus nephritis	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 lupus nephritis. The frequency of effector/memory CD4+ T lymphocytes is higher in patients with non- or partial response.; Complete response at 24 weeks: the return to within 10 percent of normal values of serum creatinine levels, proteinuria, and urine sediment.; Partial response at 24 weeks: improvement of 50 percent in all abnormal renal measurements, without worsening - within 10 percent - of any measurement	6 months
Secondary	Distinction between proliferative LN (class III and class IV) and non-proliferative LN (classes I, II and VI)		6 months
Secondary	Analysis of patient with persistent renal abnormalities as partial response		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
Secondary	Phenotype of CD8+ T cells at time point 0 predictive of clinical outcome in patients with lupus nephritis	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 lupus nephritis. The frequency of effector/memory CD8+ T lymphocytes is higher in patients with non- or partial response.	6 months
Secondary	Diagnosis of proliferative lupus nephritis in patients with systemic lupus erythematodes (SLE)	Diagnosis according to initial T cell count	6 months