Multiple SclerosisBREGSNCT04697407
IL-2 Signaling and Polarization of Regulatory LBs: Involvement in Multiple Sclerosis
A study testing Blood sampling and CSF sampling in people with Multiple Sclerosis, run by Rennes University Hospital at 1 site in France.
Trial summary
Multiple sclerosis (MS) has long been considered a disease mediated primarily by CD4+ T cells. However, recent clinical trials demonstrating significant efficacy of B-lymphocyte depletive therapies have highlighted the major role of this cell population in the development of MS. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Blood sampling and CSF sampling
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 95 participants
- Where
- 1 siteFrance
- Study dates
- 23 Mar 2021to 23 May 2023
- Phase
- Interventional
- 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- For all groups
- Pregnancy ;
- Breastfeeding ;
- Persons of full age subject to legal protection (safeguard of justice, curatorship, guardianship), persons deprived of liberty.
- Healthy volunteers :
- Absence of autoimmune pathologies
- Without immunomodulating or immunosuppressive background treatment for at least 3 months;
- Without systemic corticosteroid treatment for at least 3 months.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: BREGS - IL-2 Signaling and Polarization of Regulatory LBs: Involvement in Multiple Sclerosis
Multiple sclerosis (MS) has long been considered a disease mediated primarily by CD4+ T cells. However, recent clinical trials demonstrating significant efficacy of B-lymphocyte depletive therapies have highlighted the major role of this cell population in the development of MS. Among B-Ls, regulatory ("anti-inflammatory") B-Ls (Bregs) have protective functions in autoimmune diseases including MS, however the mechanisms that regulate the development and function of Bregs are poorly characterized. In our research laboratory (INSERM UMR1236), one of the lines of research focuses on the role of interleukin-2 (IL-2) signaling in the fate of the B lymphocyte. Numerous studies conducted in both human and mouse models of MS demonstrate the major role of this IL-2/IL2R signaling pathway in the pathogenesis of autoimmune diseases.
The hypothesis is that IL-2/IL2R pathway could contribute, by a mechanism intrinsic to B lymphocytes, to the development of autoimmune diseases such as MS.
While a defect in IL-2 signaling plays a critical role in the pathogenesis of MS, the impact of this defective signaling on regulatory B lymphocyte populations, which has been shown to play a protective role in the development of the disease, has never been studied. This study could help establish a new mechanism predisposing patients to develop the disease.
Read the detailed description
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that is the leading cause of non-traumatic disability in young adults. Pathophysiopathologically, MS has long been considered a disease mediated primarily by CD4+ T cells. However, recent clinical trials demonstrating significant efficacy of B-lymphocyte (B-lymphocyte) depletive therapies have highlighted the major role of this cell population in the development of MS. Thus, it has been shown that these cells, in addition to their ability to secrete pathogenic antibodies, produce pro-inflammatory cytokines in this disease, and an imbalance between these potentially pathogenic pro-inflammatory B-Ls and regulatory ("anti-inflammatory") B-Ls (Bregs) has been suggested.
Bregs have protective functions in autoimmune diseases including MS, however the mechanisms that regulate the development and function of Bregs are poorly characterized. In our research laboratory (INSERM UMR1236), one of the lines of research focuses on the role of interleukin-2 (IL-2) signaling in the fate of the B lymphocyte. Our team has thus demonstrated that this cytokine, essentially produced by CD4+ T lymphocytes, triggers the differentiation of naïve human B cells in vitro into plasma cells. And, more recently, the analysis of the early response of BLs in mice disabled for the IL-2 receptor specifically in mature BLs (Il2rbfl/flCD19cre/+) suggests a role of IL-2 in the acquisition of suppressive/regulatory functions. In addition, numerous studies conducted in both human and mouse models of MS demonstrate the major role of this IL-2/IL2R signaling pathway in the pathogenesis of autoimmune diseases.
The hypothesis is that IL-2 signaling induces the polarization and/or regulatory function of Bregs in vivo and that deregulation of this IL-2/IL2R pathway could contribute, by a mechanism intrinsic to B lymphocytes, to the development of autoimmune diseases such as MS.
While a defect in IL-2 signaling plays a critical role in the pathogenesis of MS, the impact of this defective signaling on regulatory B lymphocyte populations, which has been shown to play a protective role in the development of the disease, has never been studied. This study could help establish a new mechanism predisposing patients to develop the disease.
The objective of this study is the analysis of the Bregs population in the blood of MS patients (at the diagnostic stage and in different forms) who are untreated compared to controls who are healthy in various aspects.
- Conditions
- Multiple Sclerosis
- Being tested
- Blood sampling, CSF sampling
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood samplingBiological
In all groups, 80 ml of blood will be collected. For patients, this will be done during routine cares.
CSF samplingBiological
Only in both patients groups whom will have a CSF sampling in routine care, some CSF will be collected for the study in addition, with a limit of 5 ml for routine care and study.
| Study group | Role | What they receive |
|---|---|---|
| MS Patients | Experimental | Patients with MS at any stage and for any type of MS : MS at the onset of the disease, Clinically isolated syndrome (CIS), Relapsing-remitting MS (RRMS), Primary progressive MS (PPMS), Secondary progressive MS (SPMS) Receives: Biological: Blood sampling; Biological: CSF sampling |
| non MS Patients | Active comparator | Patients with a neurological and immunological disease except MS. Receives: Biological: Blood sampling; Biological: CSF sampling |
| Healthy volunteers | Active comparator | Not described Receives: Biological: Blood sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of Bregs in blood of MS patients
Comparison of the frequency of Bregs in the blood of untreated MS patients (at the diagnostic stage and in different forms of MS: Relapsing-remitting (RR), Primary Progressive (PP) and Secondary Progressive (SP)) compared to healthy controls matched for age and gender.
Measured: 1 month
Secondary outcomes (3)
Frequency of Bregs in the CSF of MS patients
Comparison of the frequency of Bregs in the CSF of early MS patients to the frequency of Bregs in the CSF of patients with other non-MS inflammatory neurological diseases.
Measured: 1 month
Comparison of IL-2, soluble IL2RA, IL-10, IL-21 and IL-5 protein concentrations
Comparison of IL-2, soluble IL2RA, IL-10, IL-21 and IL-5 protein concentrations in blood and/or CSF of MS patients to protein concentration of patients with inflammatory neurological non MS disease and to protein concentration in blood of healthy volunteers
Measured: 1 month
Comparison of the concentrations in Igs
Comparison of the concentrations in immunoglobulins in blood and/or CSF of MS patients to protein concentration of patients with inflammatory neurological non MS disease and to immunoglobulin concentration in blood of healthy volunteers
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2021
- Study start23 Mar 2021
- Primary completion23 May 2023
- Study completion23 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Rennes University HospitalThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 95 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rennes University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Laure Michel, Md, Principal investigator, Rennes University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04697407
- Sponsor's protocol ID
- 35RC20_9867_BREGS
- Acronym
- BREGS
- Status last verified
- May 2023
- First submitted
- 4 Jan 2021
- Last updated
- 24 May 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- BREGS - IL-2 Signaling and Polarization of Regulatory LBs: Involvement in Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT04697407
- Acronym / sponsor ID
- BREGS / 35RC20_9867_BREGS
- Conditions
- Multiple Sclerosis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 95 participants (actual)
- Lead sponsor
- Rennes University HospitalUniversity, hospital or other
- Study start
- 23 Mar 2021 (actual)
- Primary completion
- 23 May 2023 (actual)
- Study completion
- 23 May 2023 (actual)
- First posted
- 6 Jan 2021 (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.
Multiple sclerosis (MS) has long been considered a disease mediated primarily by CD4+ T cells. However, recent clinical trials demonstrating significant efficacy of B-lymphocyte depletive therapies have highlighted the major role of this cell population in the development of MS. Among B-Ls, regulatory ("anti-inflammatory") B-Ls (Bregs) have protective functions in autoimmune diseases including MS, however the mechanisms that regulate the development and function of Bregs are poorly characterized. In our research laboratory (INSERM UMR1236), one of the lines of research focuses on the role of interleukin-2 (IL-2) signaling in the fate of the B lymphocyte. Numerous studies conducted in both human and mouse models of MS demonstrate the major role of this IL-2/IL2R signaling pathway in the pathogenesis of autoimmune diseases.
The hypothesis is that IL-2/IL2R pathway could contribute, by a mechanism intrinsic to B lymphocytes, to the development of autoimmune diseases such as MS.
While a defect in IL-2 signaling plays a critical role in the pathogenesis of MS, the impact of this defective signaling on regulatory B lymphocyte populations, which has been shown to play a protective role in the development of the disease, has never been studied. This study could help establish a new mechanism predisposing patients to develop the disease.
Detailed description
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that is the leading cause of non-traumatic disability in young adults. Pathophysiopathologically, MS has long been considered a disease mediated primarily by CD4+ T cells. However, recent clinical trials demonstrating significant efficacy of B-lymphocyte (B-lymphocyte) depletive therapies have highlighted the major role of this cell population in the development of MS. Thus, it has been shown that these cells, in addition to their ability to secrete pathogenic antibodies, produce pro-inflammatory cytokines in this disease, and an imbalance between these potentially pathogenic pro-inflammatory B-Ls and regulatory ("anti-inflammatory") B-Ls (Bregs) has been suggested.
Bregs have protective functions in autoimmune diseases including MS, however the mechanisms that regulate the development and function of Bregs are poorly characterized. In our research laboratory (INSERM UMR1236), one of the lines of research focuses on the role of interleukin-2 (IL-2) signaling in the fate of the B lymphocyte. Our team has thus demonstrated that this cytokine, essentially produced by CD4+ T lymphocytes, triggers the differentiation of naïve human B cells in vitro into plasma cells. And, more recently, the analysis of the early response of BLs in mice disabled for the IL-2 receptor specifically in mature BLs (Il2rbfl/flCD19cre/+) suggests a role of IL-2 in the acquisition of suppressive/regulatory functions. In addition, numerous studies conducted in both human and mouse models of MS demonstrate the major role of this IL-2/IL2R signaling pathway in the pathogenesis of autoimmune diseases.
The hypothesis is that IL-2 signaling induces the polarization and/or regulatory function of Bregs in vivo and that deregulation of this IL-2/IL2R pathway could contribute, by a mechanism intrinsic to B lymphocytes, to the development of autoimmune diseases such as MS.
While a defect in IL-2 signaling plays a critical role in the pathogenesis of MS, the impact of this defective signaling on regulatory B lymphocyte populations, which has been shown to play a protective role in the development of the disease, has never been studied. This study could help establish a new mechanism predisposing patients to develop the disease.
The objective of this study is the analysis of the Bregs population in the blood of MS patients (at the diagnostic stage and in different forms) who are untreated compared to controls who are healthy in various aspects.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| MS Patients | Experimental | Biological: Blood sampling, Biological: CSF samplingPatients with MS at any stage and for any type of MS : MS at the onset of the disease, Clinically isolated syndrome (CIS), Relapsing-remitting MS (RRMS), Primary progressive MS (PPMS), Secondary progressive MS (SPMS) |
| non MS Patients | Active comparator | Biological: Blood sampling, Biological: CSF samplingPatients with a neurological and immunological disease except MS. |
| Healthy volunteers | Active comparator | Biological: Blood sampling |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (8 listed)
- For all groups
- Pregnancy ;
- Breastfeeding ;
- Persons of full age subject to legal protection (safeguard of justice, curatorship, guardianship), persons deprived of liberty.
- Absence of autoimmune pathologies
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 |
|---|---|---|
| Blood samplingIn all groups, 80 ml of blood will be collected. For patients, this will be done during routine cares. | Biological | Healthy volunteers, MS Patients, non MS Patients |
| CSF samplingOnly in both patients groups whom will have a CSF sampling in routine care, some CSF will be collected for the study in addition, with a limit of 5 ml for routine care and study. | Biological | MS Patients, non MS Patients |
Primary outcome
Frequency of Bregs in blood of MS patients
Time frame: 1 month
Comparison of the frequency of Bregs in the blood of untreated MS patients (at the diagnostic stage and in different forms of MS: Relapsing-remitting (RR), Primary Progressive (PP) and Secondary Progressive (SP)) compared to healthy controls matched for age and gender.
3 secondary outcomes
Frequency of Bregs in the CSF of MS patients
Time frame: 1 month
Comparison of IL-2, soluble IL2RA, IL-10, IL-21 and IL-5 protein concentrations
Time frame: 1 month
Comparison of the concentrations in Igs
Time frame: 1 month
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 24 May 2023.
- Individual participant dataSharing planned: No
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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.
Laure Michel, Md principal investigator
Rennes University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Blood sampling and CSF sampling in people with Multiple Sclerosis, run by Rennes University Hospital at 1 site in France.
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 0 inclusion and 8 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 24 May 2023. 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 France. 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?
Frequency of Bregs in blood of MS patients (time frame: 1 month). 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 24 May 2023.