Systemic Lupus ErythematosusNCT06327724
Belimumab in SLE Synovial Inflammation and Lymph Nodes
An observational study of Systemic Lupus Erythematosus, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
Trial summary
Systemic lupus erythematosus (SLE)is an immune-mediated inflammatory disease (IMIDs) of which the cellular and molecular alterations of the immune system driving the diseases still remains largely unknown. Accordingly, it remains difficult to predict the individual patient's response to treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Systemic Lupus Erythematosus
- What is being tested?
- Belimumab
- How many people
- 15 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Sep 2023to 1 Mar 2025
- 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: SLE patients
Who may be able to join
- SLE patients who:
- fulfill ACR 1997 and/or SLICC and/or ACR/ EULAR 2019 criteria,
- have active joint disease (arthritis) in wrist, knee or ankle joints.
- have a SLEDAI-2K score ≥6.
- are aged between 18-75
- start with belimumab or any other immunosuppressive treatment
Who cannot join
- Patients who are not able to give informed consent.
- Pregnancy
- Severe renal impairment (eGFR <30ml/min/1.73m2)
- Active nephritis
- Present or previous treatment with any cell depleting therapies, including anti-B-cell therapy or other investigational agents
- Intravenous cyclophosphamide 90 days prior to belimumab
Show all 13Show fewer
- Any non-biologic investigational agent 30 Days Prior to belimumab (or 5 half-lives, whichever is greater)
- Live vaccines within 30 days prior to baseline or concurrently with belimumab
- Presence of any other disease for which study subjects need chronic or intermittent immunosuppressive therapy (e.g. prednisolon for COPD).
- History of malignancies neoplasm within the last 5 years except basal cell or squamous cell carcinoma of the skin treated with local resection only or carcinoma in situ of the uterine cervix treated locally and with no evidence of metastatic disease for 3 years
- Have any intercurrent significant medical or psychiatric illness that the investigator considers would make the candidate unsuitable for the study, including evidence of serious suicide risk including any history of suicidal behaviour in the last 6 months and/or any suicidal ideation in the last 2 months or who in the investigator's judgment, poses a significant suicide risk
- Have current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within 365 days prior to Day 0
- Have a historically positive HIV test or test positive at screening for HIV, or other immunodeficiency
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
Amsterdam UMC; location Academic Medical Center
Amsterdam, 1100DD
Sander W Tas, Prof. dr., +31 20 56 67765, secr-reumatologie@amsterdamumc.nl
About this study
Official title: The Effects of Belimumab on Synovial Inflammation and Composition of Lymph Nodes in SLE Patients
Systemic lupus erythematosus (SLE)is an immune-mediated inflammatory disease (IMIDs) of which the cellular and molecular alterations of the immune system driving the diseases still remains largely unknown. Accordingly, it remains difficult to predict the individual patient's response to treatment. Moreover, the patient's response to treatment remains heterogeneous and difficult to predict, despite the development of a variety of novel and powerful drugs (including the so-called biologicals). Therefore, there is a clear need for the identification and validation of cellular and molecular biomarkers which can provide useful clinical information for diagnosis, classification, prognosis and treatment, as well as the development of new therapeutic strategies. Biomarkers can be found and analyzed in different body compartments, of which the peripheral blood and the intra-articular synovial fluid or tissue are most easily accessible. However, previous studies in RA and other IMIDs showed that adaptive immune responses in other tissues such as lymph nodes also play an important role. Investigating other immune compartments of the body such as the lymph nodes could result in new insights. To study the early pathogenesis of inflammatory conditions, in 2008 our department initiated core-needle inguinal lymph node biopsy sampling. Since then more than 100 lymph node biopsy procedures were performed. The procedure is well-tolerated and, other than a small hematoma which does not require therapy in most of the cases, no complications were reported.
In the current study, the effects of belimumab (anti-BAFF) in SLE will be investigated by studying the immune alterations taking place in lymph nodes in comparison to peripheral blood and immune alterations taking place in the end-organ, e.g. the joint (wrist, knee or ankle) by taking synovial biopsies during a needle- or mini-arthroscopy. This procedure has been performed frequently in our department over the last 15 years. In this way immune alterations in the lymph nodes (secondary lymphoid organ), peripheral blood (systemic) and the joint (end organ for the disease) will be assessed and compared.
Read the detailed description
The primary goal of this study is to investigate the effects of belimumab on the composition of lymph nodes and the inflamed synovial tissue as well as (subsets of) immune cells in the peripheral blood using advanced flow cytometry methods. In addition, immunological alterations in lymphoid tissue and inflamed synovial tissue of SLE patients will be identified and correlated with disease stage/phenotype, prognosis, and belimumab treatment response. In this way novel biomarkers may be identified and validated that can be used for personalized medicine in SLE.
The specific types of immunological alterations that will be studied include:
- Genetic, epigenetic and transcriptional alterations of immune cells and stromal cells, including single cell RNA sequencing (scRNAseq)
- TCR and BCR repertoire
- Phenotype and function of (auto-reactive) T and B cells
- Cytokine production by immune cells and stromal cells
- Signalling events in immune cells and stromal cells
- Antigen presentation by immune cells and stromal cells
All of these parameters will be compared between lymph nodes, blood and synovium (if applicable) in SLE patients before and after belimumab treatment.
Research Hypothesis Patients with SLE contain activated immune cells in their lymph nodes and inflamed synovial tissue. Furthermore, activation of stromal cells such as fibroblasts and endothelial cells may also be increased compared to (historical) healthy controls. In addition, dominant T cell and B cell clones may be present. Belimumab treatment will result in reduced inflammation in the synovial tissue and perhaps even normalization of lymph node architecture.
- Conditions
- Systemic Lupus Erythematosus
- Being tested
- Belimumab
- Keywords
- lymph node, synovial tissue
- Medical subject headings
- Lupus Erythematosus, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BelimumabDrug
Also called Any other treatment
Start of new treatment due to active disease
What is being measured
The primary outcome is the main question the study is designed to answer.
Differences in lymph node cellular composition as assessed by advanced flow cytometry
Differences in lymph node cellular composition and functional aspects in SLE patients after belimumab treatment compared to SLE patients starting any other effective treatment.
Measured: 4 weeks
Secondary outcomes (2)
Differences in peripheral blood cellular composition as assessed by advanced flow cytometry
Differences in peripheral blood cellular composition and functional aspects in SLE patients after belimumab treatment compared to SLE patients starting any other effective treatment.
Measured: 4 weeks
Differences in synovial tissue cellular composition as assessed by advanced flow cytometry
Differences in synovial tissue cellular composition and functional aspects in SLE patients after belimumab treatment compared to SLE patients starting any other effective treatment.
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2024
- Study start1 Sep 2023
- Primary completion1 Jan 2025 (estimated)
- Study completion1 Mar 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Systemic Lupus ErythematosusStudies of the same condition, open and under way.
- More trials run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)The 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Responsible party
- Principal investigator, Sander Tas, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06327724
- Sponsor's protocol ID
- 12434
- Status last verified
- Mar 2024
- First submitted
- 13 Mar 2024
- Last updated
- 25 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Belimumab on Synovial Inflammation and Composition of Lymph Nodes in SLE Patients
- ClinicalTrials.gov ID
- NCT06327724
- Acronym / sponsor ID
- 12434
- Conditions
- Systemic Lupus Erythematosus
- Keywords
- lymph node, synovial tissue
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- 1 Sep 2023 (actual)
- Primary completion
- 1 Jan 2025 (estimated)
- Study completion
- 1 Mar 2025 (estimated)
- First posted
- 25 Mar 2024 (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.
Systemic lupus erythematosus (SLE)is an immune-mediated inflammatory disease (IMIDs) of which the cellular and molecular alterations of the immune system driving the diseases still remains largely unknown. Accordingly, it remains difficult to predict the individual patient's response to treatment. Moreover, the patient's response to treatment remains heterogeneous and difficult to predict, despite the development of a variety of novel and powerful drugs (including the so-called biologicals). Therefore, there is a clear need for the identification and validation of cellular and molecular biomarkers which can provide useful clinical information for diagnosis, classification, prognosis and treatment, as well as the development of new therapeutic strategies. Biomarkers can be found and analyzed in different body compartments, of which the peripheral blood and the intra-articular synovial fluid or tissue are most easily accessible. However, previous studies in RA and other IMIDs showed that adaptive immune responses in other tissues such as lymph nodes also play an important role. Investigating other immune compartments of the body such as the lymph nodes could result in new insights. To study the early pathogenesis of inflammatory conditions, in 2008 our department initiated core-needle inguinal lymph node biopsy sampling. Since then more than 100 lymph node biopsy procedures were performed. The procedure is well-tolerated and, other than a small hematoma which does not require therapy in most of the cases, no complications were reported.
In the current study, the effects of belimumab (anti-BAFF) in SLE will be investigated by studying the immune alterations taking place in lymph nodes in comparison to peripheral blood and immune alterations taking place in the end-organ, e.g. the joint (wrist, knee or ankle) by taking synovial biopsies during a needle- or mini-arthroscopy. This procedure has been performed frequently in our department over the last 15 years. In this way immune alterations in the lymph nodes (secondary lymphoid organ), peripheral blood (systemic) and the joint (end organ for the disease) will be assessed and compared.
Detailed description
The primary goal of this study is to investigate the effects of belimumab on the composition of lymph nodes and the inflamed synovial tissue as well as (subsets of) immune cells in the peripheral blood using advanced flow cytometry methods. In addition, immunological alterations in lymphoid tissue and inflamed synovial tissue of SLE patients will be identified and correlated with disease stage/phenotype, prognosis, and belimumab treatment response. In this way novel biomarkers may be identified and validated that can be used for personalized medicine in SLE.
The specific types of immunological alterations that will be studied include:
- Genetic, epigenetic and transcriptional alterations of immune cells and stromal cells, including single cell RNA sequencing (scRNAseq)
- TCR and BCR repertoire
- Phenotype and function of (auto-reactive) T and B cells
- Cytokine production by immune cells and stromal cells
- Signalling events in immune cells and stromal cells
- Antigen presentation by immune cells and stromal cells
All of these parameters will be compared between lymph nodes, blood and synovium (if applicable) in SLE patients before and after belimumab treatment.
Research Hypothesis Patients with SLE contain activated immune cells in their lymph nodes and inflamed synovial tissue. Furthermore, activation of stromal cells such as fibroblasts and endothelial cells may also be increased compared to (historical) healthy controls. In addition, dominant T cell and B cell clones may be present. Belimumab treatment will result in reduced inflammation in the synovial tissue and perhaps even normalization of lymph node architecture.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- SLE patients
Key inclusion criteria (6 listed)
- fulfill ACR 1997 and/or SLICC and/or ACR/ EULAR 2019 criteria,
- have active joint disease (arthritis) in wrist, knee or ankle joints.
- have a SLEDAI-2K score ≥6.
- are aged between 18-75
- start with belimumab or any other immunosuppressive treatment
Key exclusion criteria (13 listed)
- Patients who are not able to give informed consent.
- Pregnancy
- Severe renal impairment (eGFR <30ml/min/1.73m2)
- Active nephritis
- Present or previous treatment with any cell depleting therapies, including anti-B-cell therapy or other investigational agents
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 |
|---|---|---|
| BelimumabAlso: Any other treatmentStart of new treatment due to active disease | Drug | – |
Primary outcome
Differences in lymph node cellular composition as assessed by advanced flow cytometry
Time frame: 4 weeks
Differences in lymph node cellular composition and functional aspects in SLE patients after belimumab treatment compared to SLE patients starting any other effective treatment.
2 secondary outcomes
Differences in peripheral blood cellular composition as assessed by advanced flow cytometry
Time frame: 4 weeks
Differences in synovial tissue cellular composition as assessed by advanced flow cytometry
Time frame: 4 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2024.
- Individual participant dataSharing planned: Undecided
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Systemic Lupus Erythematosus, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
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 6 inclusion and 13 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: status not confirmed, as of the sponsor's last update on 25 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sander W Tas, Prof. dr. (+31 20 56 67765, secr-reumatologie@amsterdamumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Differences in lymph node cellular composition as assessed by advanced flow cytometry (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 25 Mar 2024.