Glomerulonephritis AcutePRE-FLAREDNCT04428398
Urinary T Lymphocytes Predict Renal Flares in Patients With Inactive ANCA-associated Glomerulonephritis
An observational study of Glomerulonephritis Acute, run by Charite University, Berlin, Germany at 2 sites in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glomerulonephritis Acute
- What is being tested?
- Analysis of urine samples with flow cytometry
- How many people
- 100 participants
- Where
- 2 sitesGermany
- Study dates
- 1 May 2020to 1 Sep 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients in medical wards or at outpatient departments of 2 facilities: * Charité - Universitätsmedizin Berlin * Helios Klinikum Berlin-Buch
Who may be able to join
- 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
Who cannot join
- urinary tract infection
- active menstrual bleeding
- active renal involvement
- other active renal disease (e.g. diabetic nephropathy)
- Initially, we defined treatment with rituximab as exclusion criteria. However, upon closer examination, we recognized that this exclusion criterion was overly restrictive and may have inadvertently excluded eligible participants who met our other inclusion criteria. As a result of this reassessment, we have revised our exclusion criteria to no longer exclude individuals solely on the basis of receiving rituximab treatment.
Trial locations and contacts
2 sites in 1 country.
Germany2 sites
Charité - Universitätsmedizin Berlin
Berlin, 10117
Helios Klinikum Berlin-Buch
Berlin, 13125
About this study
Official title: Urinary T Lymphocytes Predict Renal Flares in Patients With Inactive Anti-neutrophil Cytoplasmic Antibody (ANCA) Associated Glomerulonephritis
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.
Read the 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.
- Conditions
- Glomerulonephritis Acute
- Being tested
- Analysis of urine samples with flow cytometry
- Keywords
- Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Pauci-Immune Glomerulonephritis, urinary biomarker, Churg-Strauss Syndrome, Microscopic Polyangiitis, Granulomatosis with Polyangiitis, effector memory T lymphocytes, prediction
- Medical subject headings
- Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Churg-Strauss Syndrome, Microscopic Polyangiitis, Granulomatosis with Polyangiitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Analysis of urine samples with flow cytometryDiagnostic 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
| Study group | Role | What they receive |
|---|---|---|
| No renal involvement | Patients with ANCA-vasculitis and no ANCA-associated renal involvement in disease history Receives: Diagnostic Test: Analysis of urine samples with flow cytometry | |
| Renal remission | Patient with ANCA-vasculitis in renal remission Receives: Diagnostic Test: Analysis of urine samples with flow cytometry |
What is being measured
The primary outcome is the main question the study is designed to answer.
Prediction of renal relapse after six months depending initial CD4+ count
- 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)
Measured: 6 months
Secondary outcomes (5)
Prediction of renal relapse after six months depending initial CD8+ count
Measured: 6 months
Prediction of renal relapse after six months depending initial CD4+/CD8+ subsets
Subsets: T effector memory cells (CD45RO+/CCR7-)
Measured: 6 months
Prediction of renal relapse after 12 months depending initial CD4+ count
Measured: 12 months
Prediction of renal relapse after 12 months depending initial CD8+ count
Measured: 12 months
Prediction of renal relapse after 12 months depending initial CD4+/CD8+ subsets
Subsets: T effector memory cells (CD45RO+/CCR7-)
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2020
- Study start1 May 2020
- Primary completion1 Sep 2021
- Study completion1 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Glomerulonephritis AcuteStudies of the same condition, open and under way.
- More trials run by Charite University, Berlin, GermanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Charite University, Berlin, Germany
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Philipp Enghard, Charite University, Berlin, Germany
- Investigators
- Philipp Enghard, Principal investigator, Charite University, Berlin, GermanyAdrian Schreiber, PD Dr. med., Principal investigator, Charite University, Berlin, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04428398
- Sponsor's protocol ID
- PRE-FLARED
- Acronym
- PRE-FLARED
- Status last verified
- Nov 2023
- First submitted
- 9 Jun 2020
- Last updated
- 14 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Goceroglu A, Berden AE, Fiocco M, Flossmann O, Westman KW, Ferrario F, Gaskin G, Pusey CD, Hagen EC, Noel 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.
PubMed 27973575Menez 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.
PubMed 30472700Cordova-Sanchez BM, Mejia-Vilet JM, Morales-Buenrostro LE, Loyola-Rodriguez 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.
PubMed 26852317Enghard 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.
PubMed 23475982Abdulahad 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.
PubMed 19714581Prskalo L, Skopnik CM, Goerlich N, Freund P, Wagner L, Grothgar E, Mirkheshti P, Klocke J, Sonnemann J, Metzke D, Schneider U, Hiepe F, Eckardt KU, Salama AD, Bieringer M, Schreiber A, Enghard P. Urinary CD4 + T Cells Predict Renal Relapse in ANCA-Associated Vasculitis. J Am Soc Nephrol. 2024 Apr 1;35(4):483-494. doi: 10.1681/ASN.0000000000000311. Epub 2024 Jan 17.
PubMed 38231590
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Urinary T Lymphocytes Predict Renal Flares in Patients With Inactive Anti-neutrophil Cytoplasmic Antibody (ANCA) Associated Glomerulonephritis
- ClinicalTrials.gov ID
- NCT04428398
- Acronym / sponsor ID
- PRE-FLARED / PRE-FLARED
- Conditions
- Glomerulonephritis Acute
- Keywords
- Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Pauci-Immune Glomerulonephritis, urinary biomarker, Churg-Strauss Syndrome, Microscopic Polyangiitis, Granulomatosis with Polyangiitis, effector memory T lymphocytes, prediction
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Charite University, Berlin, GermanyUniversity, hospital or other
- Study start
- 1 May 2020 (actual)
- Primary completion
- 1 Sep 2021 (actual)
- Study completion
- 1 Sep 2021 (actual)
- First posted
- 11 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| No renal involvement | – | Diagnostic Test: Analysis of urine samples with flow cytometryPatients with ANCA-vasculitis and no ANCA-associated renal involvement in disease history |
| Renal remission | – | Diagnostic Test: Analysis of urine samples with flow cytometryPatient with ANCA-vasculitis in renal remission |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients in medical wards or at outpatient departments of 2 facilities: * Charité - Universitätsmedizin Berlin * Helios Klinikum Berlin-Buch
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (5 listed)
- urinary tract infection
- active menstrual bleeding
- active renal involvement
- other active renal disease (e.g. diabetic nephropathy)
- Initially, we defined treatment with rituximab as exclusion criteria. However, upon closer examination, we recognized that this exclusion criterion was overly restrictive and may have inadvertently excluded eligible participants who met our other inclusion criteria. As a result of this reassessment, we have revised our exclusion criteria to no longer exclude individuals solely on the basis of receiving rituximab treatment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Analysis of urine samples with flow cytometryUrine 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 | Diagnostic test | No renal involvement, Renal remission |
Primary outcome
Prediction of renal relapse after six months depending initial CD4+ count
Time frame: 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)
5 secondary outcomes
Prediction of renal relapse after six months depending initial CD8+ count
Time frame: 6 months
Prediction of renal relapse after six months depending initial CD4+/CD8+ subsets
Time frame: 6 months
Prediction of renal relapse after 12 months depending initial CD4+ count
Time frame: 12 months
Prediction of renal relapse after 12 months depending initial CD8+ count
Time frame: 12 months
Prediction of renal relapse after 12 months depending initial CD4+/CD8+ subsets
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2023.
- Background: PubMed 27973575Goceroglu A, Berden AE, Fiocco M, Flossmann O, Westman KW, Ferrario F, Gaskin G, Pusey CD, Hagen EC, Noel 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.
- Background: PubMed 30472700Menez 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.
- Background: PubMed 26852317Cordova-Sanchez BM, Mejia-Vilet JM, Morales-Buenrostro LE, Loyola-Rodriguez 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.
- Background: PubMed 23475982Enghard 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.
- Background: PubMed 19714581Abdulahad 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.
- Derived from this study: PubMed 38231590Prskalo L, Skopnik CM, Goerlich N, Freund P, Wagner L, Grothgar E, Mirkheshti P, Klocke J, Sonnemann J, Metzke D, Schneider U, Hiepe F, Eckardt KU, Salama AD, Bieringer M, Schreiber A, Enghard P. Urinary CD4 + T Cells Predict Renal Relapse in ANCA-Associated Vasculitis. J Am Soc Nephrol. 2024 Apr 1;35(4):483-494. doi: 10.1681/ASN.0000000000000311. Epub 2024 Jan 17.
- Individual participant dataSharing planned: Yes
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Philipp Enghard principal investigator
Charite University, Berlin, Germany
Adrian Schreiber, PD Dr. med. principal investigator
Charite University, Berlin, Germany
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Glomerulonephritis Acute, run by Charite University, Berlin, Germany at 2 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Prediction of renal relapse after six months depending initial CD4+ count (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04428398, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2023; AzTrials last refreshed its copy on 26 Oct 2026.