Immune regulation by dimethylfumarate (DMF) in patients with relapsing Remitting Multiple Sclerosis.

Immune regulation by dimethylfumarate (DMF) in patients with relapsing Remitting Multiple Sclerosis. - Dimethylfumarate by patients with MS

Status

Recruiting

Phases

Phase 4

Study type

Observational

Source

NL-OMON

Registry ID

NL-OMON41017

Enrollment

Registered

2014-10-31

Start date

2014-12-04

Completion date

Unknown

Last updated

2024-04-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Multiple Sclerosis

Interventions

None listed

Eligibility

Age

18 Years to 99 Years

Inclusion criteria

Inclusion criteria: Relapsing Remitting Multiple Sclerose according to 2010 revised McDonald criteria Age > 18 years Disease duration

Exclusion criteria

Exclusion criteria: Relapse

Design outcomes

Primary

Measure	Time frame
-Effect of DMF treatment on Treg function as assessed in an in vitro, carboxyfluorescein succinimidyl ester (CFSE)-based proliferation suppression assay: to assess suppressive capacity of Tregs (CD4+CD25+CD127- T lymphocytes) we will use a proliferation suppression assay, in which responder T cells are cultured with varying amounts of T regs (Treg/Tresp ratio*s).(18;42) Treg normally suppress the proliferation of activated Tresps, but this pathway is defective in MS patients and might be restored by DMF. -Effect of DMF treatment on Treg numbers as assessed by flow cytometry. After isolation, PBMC will be directly incubated with fluorescently labeled monoclonal antibodies which are directed against cell-subset-specific CD markers (CD4+CD25+CD127-FoxP3+) -Effect of DMF treatment on Breg differentiation, i.e. IL-10 producing B cells after CpG stimulation: phenotypical analysis will be performed by intracellular flow cytometry, measuring frequencies of IL-10 producing B cells upon in vitro culture in the presence of CpG, a TLR-9 agonist.(23) The Breg frequency in MS patients is strongly reduced and may be restored by DMF treatment.	—

Measure

Time frame

-Effect of DMF treatment on Treg function as assessed in an in vitro, carboxyfluorescein succinimidyl ester (CFSE)-based proliferation suppression assay: to assess suppressive capacity of Tregs (CD4+CD25+CD127- T lymphocytes) we will use a proliferation suppression assay, in which responder T cells are cultured with varying amounts of T regs (Treg/Tresp ratio*s).(18;42) Treg normally suppress the proliferation of activated Tresps, but this pathway is defective in MS patients and might be restored by DMF. -Effect of DMF treatment on Treg numbers as assessed by flow cytometry. After isolation, PBMC will be directly incubated with fluorescently labeled monoclonal antibodies which are directed against cell-subset-specific CD markers (CD4+CD25+CD127-FoxP3+) -Effect of DMF treatment on Breg differentiation, i.e. IL-10 producing B cells after CpG stimulation: phenotypical analysis will be performed by intracellular flow cytometry, measuring frequencies of IL-10 producing B cells upon in vitro culture in the presence of CpG, a TLR-9 agonist.(23) The Breg frequency in MS patients is strongly reduced and may be restored by DMF treatment.

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Secondary

Measure	Time frame
-T cell subset analysis based on intracellular cytokine expression as evaluated by flow cytometry (IL-10, IL-4, IL-17, IFN-, TNF- and GM-CSF); changes in the cytokine profiles will be associated with changes in Treg and Breg. -Clinical outcome parameters such as the Kurtzke Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), relapse rate and Fatigue Scale for Motor and Cognitive Functions (FSMC) will be associated with changes in Treg and Breg.	—

Measure

Time frame

-T cell subset analysis based on intracellular cytokine expression as evaluated by flow cytometry (IL-10, IL-4, IL-17, IFN-*, TNF-* and GM-CSF); changes in the cytokine profiles will be associated with changes in Treg and Breg. -Clinical outcome parameters such as the Kurtzke Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), relapse rate and Fatigue Scale for Motor and Cognitive Functions (FSMC) will be associated with changes in Treg and Breg.

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Countries

Netherlands

Outcome results