Clinical trial NCT04320797: Urinary T Cell Biomarker for Prediction in Lupus Nephritis
Official title: Phenotype of Urinary CD4+ T Cells as Biomarkers for Prediction of Outcome in Lupus Nephritis
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Lupus Nephritis
Keywords: lupus nephritis
systemic lupus erythematodes
urinary biomarker
outcome
prediction
urinary effector memory T lymphocytes
glomerulonephritis
non-invasive biomarker
flow cytometry
treatment outcome
CD4-positive T-lymphocytes/immunology
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: Berlin Institute of Health
First posted: 2020-03-25
Enrollment: 79
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients at medical wards of Charité Universitätsmedizin Berlin and University College London

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Phenotype of CD4+ T cells at time point 0 predictive of clinical outcome in patients with lupus nephritis
timeFrame: 6 months
Secondary outcomes:
measure: Distinction between proliferative LN (class III and class IV) and non-proliferative LN (classes I, II and VI)
timeFrame: 6 months
measure: Analysis of patient with persistent renal abnormalities as partial response
timeFrame: 6 months
measure: Prediction of complete or partial response according to normalization of the amount of urinary T cells at time point 2 and 4
timeFrame: 6 months
measure: Phenotype of CD8+ T cells at time point 0 predictive of clinical outcome in patients with lupus nephritis
timeFrame: 6 months
measure: Diagnosis of proliferative lupus nephritis in patients with systemic lupus erythematodes (SLE)
timeFrame: 6 months
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: London
country: United Kingdom
facility: The Royal Free London
Study officials:
affiliation: Charite University, Berlin, Germany
name: Philipp Enghard, PD Dr. med.
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.
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.
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(1):94. doi: 10.1186/s13075-015-0600-y.