Systemic Lupus Erythematosus Clinical Trial
Official title:
Whole Blood Transcriptional and Mass Cytometry Immune Profiling in Systemic Lupus Erythematosus (SLE) Patients to Discern the Salutary Effects of Belimumab on Halting Disease Progression and Flares Without Compromising Host Fitness
NCT number | NCT04570306 |
Other study ID # | DB11 |
Secondary ID | |
Status | Completed |
Phase | |
First received | |
Last updated | |
Start date | December 16, 2020 |
Est. completion date | December 16, 2023 |
Verified date | June 2024 |
Source | Biomedical Research Foundation, Academy of Athens |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Observational |
The investigators propose to perform RNA-sequencing of the whole blood initially, in a cohort of 80 SLE patients who will receive belimumab as part of standard clinical practice, in order to assess intra-patient longitudinal (baseline, 1, 3 and 6 months) transcriptome changes and examine whether treatment can ameliorate the activity/flare, severity and major organ disease gene signatures. The investigators will also obtain preliminary information on molecular signatures predicting clinical responses and the impact of belimumab on gene signatures of host defense against viral and bacterial (including mycobacterial) pathogens. Using modules of cell type-specific genes and co-expression gene networks, The investigators will deconvolute our data to define pertinent molecular alterations in specific immune cell types. Results will be validated and functionally characterized by single-cell mass cytometry (performed at the aforementioned time points), which enables investigation of the cell identity (including subsets of B-cells and myeloid cells of particular relevance to the disease) and activation status at protein level (e.g. phosphorylation) through next-generation, high-dimensional flow cytometry. Through a focused analysis followed by targeted gene expression and function studies in purified monocytes, the investigators will determine whether belimumab can restore "SLE-primed" monocytes thus, alleviating their inflammatory and pro-atherogenic phenotype and enhancing their bactericidal activity. Collectively, these studies will provide novel mechanistic insights on the beneficial efficacy/toxicity ratio of belimumab therapy in SLE.
Status | Completed |
Enrollment | 85 |
Est. completion date | December 16, 2023 |
Est. primary completion date | December 16, 2023 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 65 Years |
Eligibility | Inclusion Criteria: SLE patients: - who meet the Systemic Lupus International Collaborating Clinics (SLICC) 2012 and/or European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) 2019 classification criteria; - have active disease defined as the combination of clinical (i.e., excluding serology) SLEDAI-2000 =6 and/or physician global assessment (PhGA) =1.5. Both flaring (acute exacerbation) and persistent disease activity will be considered; - are started belimumab (standard approved dose of i.v. 10 mg/kg or subcutaneous 200 mg/week) due to active disease. The intention to start belimumab will be made by the treating Rheumatologist(s), in accordance to the current standard of care, and on the basis of shared physician-patient decision making. Exclusion Criteria: - age <18 years - co-existing rheumatic or other autoimmune disease - pregnancy - active infection - history of malignant disorder |
Country | Name | City | State |
---|---|---|---|
Greece | BRFAA | Athens |
Lead Sponsor | Collaborator |
---|---|
Biomedical Research Foundation, Academy of Athens | Attikon University General Hospital, Athens, GlaxoSmithKline, University Hospital of Heraklion |
Greece,
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Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Changes in blood transcriptome in relation to clinical response induced by belimumab | To evaluate changes in SLE blood transcriptome that are induced by treatment with belimumab with emphasis on the reversibility of previously-defined gene signatures for disease activity/flare, severity/progression and major organ involvement. Results will be correlated with validated patient outcomes such as clinical response (defined according to SLE Responder Index-4). | 1, 3 and 6 months | |
Secondary | Changes in blood transcriptome in relation to low disease activity induced by belimumab | To evaluate changes in SLE blood transcriptome that are induced by treatment with belimumab with emphasis on the reversibility of previously-defined gene signatures for disease activity/flare, severity/progression and major organ involvement. Results will be correlated with low disease activity in SLE (according to the Low Disease Activity State definition) | 3 and 6 months | |
Secondary | Changes in blood transcriptome in relation to remission induced by belimumab | To evaluate changes in SLE blood transcriptome that are induced by treatment with belimumab with emphasis on the reversibility of previously-defined gene signatures for disease activity/flare, severity/progression and major organ involvement. Results will be correlated with remission in SLE (according to the Definition of Remission [DORIS] in SLE) | 6 months |
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