Multiple Sclerosis, Relapsing-RemittingPhase 4DIMAT-MSNCT02461069
Investigation of the Effect of Dimethyl Fumarate on T Cells in Patients With Relapsing Remitting Multiple Sclerosis
A Phase 4 study testing Dimethyl fumarate in people with Multiple Sclerosis, Relapsing-Remitting, run by University Hospital Muenster at 6 sites in Germany.
Trial summary
This is an exploratory study, which allows analysis of multiple immune parameters derived from peripheral blood mononuclear cells (PBMCs) from patients with relapsing remitting multiple sclerosis before and during immune-modulatory treatment with dimethyl fumarate in comparison to PBMCs from healthy subjects. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Multiple Sclerosis, Relapsing-Remitting
- What is being tested?
- Dimethyl fumarate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 67 participants
- Where
- 6 sitesGermany
- Study dates
- 6 May 2015to 7 May 2018
- Phase
- Phase 4
- 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 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy subjects:
- H-1. Written informed consent must be obtained before any assessment is performed.
- H-2. Male and female subjects aged 18 - 60 years.
- H-3. No history of multiple sclerosis or clinically isolated syndrome.
- H-4. No history of other autoimmune diseases, which has been treated systemically with corticosteroids, immunomodulators or immunosuppressive drugs at any time point.
- RRMS patients:
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- MS-1. Written informed consent must be obtained before any assessment is performed.
- MS-2. Male and female subjects aged 18 - 60 years.
- MS-3. Patients with RRMS, defined by 2010 revised McDonald criteria.
- MS-4. Patients with an Expanded Disability Status Scale (EDSS) score of 0-6.0.
- MS-5. Patients with one of the following treatment status:
- Naïve to disease modifying (DM) treatment (i.e. no DM treatment for at least 1 month),
- Currently on MS therapy with interferon β-1 or glatiramer acetate and willing to switch to dimethyl fumarate (Tecfidera®).
- MS-6. MRI-scan of the brain ≤ 3 months at screening.
Who cannot join
- RRMS patients:
- MS-1. Known hypersensitivity to dimethyl fumarate or any ingredients of Tecfidera® (microcrystalline cellulose; croscarmellose-sodium; talcum; high dispersion, hydrophobic silicon dioxide; magnesiumstearate (Ph. Eur.); triethylcitrate; methacrylic acid-methacrylate copolymer (1:1) (Ph. Eur.); methacrylic acid-ethylacrylate copolymer (1:1)-dispersion 30% (Ph. Eur.), simeticon, sodiumdodecylsulfate, polysorbate 80, gelantine, titanium oxide (E171), brilliant blue (E133), hydrated Iron(III)-oxide hydroxide (E172), shellac, potassium hydroxide.
- MS-2. A MS-relapse within 30 days prior to screening.
- MS-3. Known history of active tuberculosis or active tuberculosis determined by a positive QuantiFERON® TB Gold test (i.e. a negative test result has to be provided at screening unless a negative test result exists from the last 3 months prior to screening).
- MS-4. Moderate to severe impairment of liver function or persisting elevations > 2 x ULN (confirmed by retest) of serum glutamic pyruvic transaminase/ alanine aminotransferase (SGPT/ALT) or serum glutamic oxaloacetic transaminase/aspartate aminotransferase (SGOT/AST), except patients with confirmed Gilbert´s syndrome (Meulengracht´s disease).
- MS-5. Moderate to severe impairment of renal function, as shown by serum creatinine > 133 μmol/L (or > 1.5 mg/dL).
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- MS-6. Patients with significantly impaired bone marrow function or significant anemia, leukopenia, neutropenia or thrombocytopenia.
- MS-7. Women of childbearing potential not utilizing highly effective contraception.
- Both populations:
- MS/H-1. Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study.
- MS/H-2. Subjects unlikely to comply with protocol as determined by investigator, e.g., uncooperative attitude, inability to return for follow-up visits (e.g. major physical disability), and known unlikelihood of completing the study.
- MS/H-3. Clinically relevant cardiovascular, neurological, endocrine, or other major systemic disease making implementation of the protocol or interpretation of the study results difficult or that would put the subject at risk by participating in the study.
- MS/H-4. Subjects with ulcerative colitis or Crohn´s disease.
- MS/H-5. Subjects with a congenital or acquired severe immunodeficiency, a history of cancer (except for basal or squamous cell skin lesions which have been surgically excised, with no evidence of metastasis), lymph proliferative disease, or any subject who has received lymphoid irradiation.
- MS/H-6. Human immunodeficiency virus (HIV) positive, hepatitis B virus positive or hepatitis C virus positive subjects (i.e. a negative test result has to be provided at screening. In the presence of a negative test result from the last 3 months prior to screening, the test has not to be repeated at screening.).
- MS/H-7. Acute or chronic infection.
- MS/H-8. History of drug or alcohol abuse.
- MS/H-9. Use of adrenocorticotrophic hormone (ACTH) or systemic corticosteroids for 4 weeks prior to screening.
- MS/H-10. Prior or concomitant use of cytokine therapy or intravenous immunoglobulins in the 3 months prior to screening.
- MS/H-11. Prior use of alemtuzumab or cladribine.
- MS/H-12. Prior use (within 1 year) of fingolimod (Gilenya®) or natalizumab (Tysabri®).
- MS/H-13. Prior use (within 2 years) of mitoxantrone, or other immunosuppressant agents such as azathioprine, cyclophosphamide, cyclosporine, methotrexate or mycophenolate mofetil.
- MS/H-14. Prior treatment with teriflunomide or leflunomide, unless successful wash-out, confirmed by plasma concentration of < 0.02 μg/ml.
- MS/H-15. Prior use of any investigational drug in the 6 months preceding screening.
- MS/H-16. Pregnant or breast-feeding women.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Germany6 sites
Neurologisches Studienzentrum Dr. Schmidt/Dr. Neudecker/ Dr. Viehbahn/Dr. Kronenberger
Bonn, 53111
Neurologische Gemeinschaftspraxis im Bienenkorbhaus
Frankfurt am Main, 60313
Neurologische Univ.-Klinik
Heidelberg, 69120
Klinik und Poliklinik für Neurologie, Universitätsklinikum Mainz
Mainz, 55131
University Hospital Muenster, Department of Neurology
Münster, 48149
MVZ-Neurologie Klinikum Osnabrück GmbH
Osnabrück, 49076
About this study
Official title: A 24-week, Multicenter, Exploratory, Two Arm Study to Assess the Effect of Dimethyl Fumarate on Immune-Modulatory Action on T Cells in Patients With Relapsing Remitting Multiple Sclerosis (DIMAT-MS)
This is an exploratory study, which allows analysis of multiple immune parameters derived from peripheral blood mononuclear cells (PBMCs) from patients with relapsing remitting multiple sclerosis before and during immune-modulatory treatment with dimethyl fumarate in comparison to PBMCs from healthy subjects.
Read the detailed description
The purpose of the trial is to shed more light on the mechanisms of action of dimethyl fumarate in patients with relapsing remitting multiple sclerosis. More specifically the influence of dimethyl fumarate on peripheral immune cells will be addressed to evaluate changes in cytokine production by the distinct T cell subsets and the differentiation capacity of naïve T cells. Furthermore, the impact of dimethyl fumarate treatment on the migratory capacity of T cells as well as the evaluation of changes in the suppressive capacity of regulatory T cells will be evaluated. To put the obtained results into context, response data of dimethyl fumarate-treated patients will be compared with data from healthy subjects.
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Being tested
- Dimethyl fumarate
- Keywords
- dimethyl fumarate
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dimethyl fumarateDrug
Also called Tecfidera®
Dimethyl fumarate (Tecfidera®) treatment is initiated by daily administration of 120 mg Tecfidera® p.o. in the morning in week 0. At week 1, the dose is increased to 120 mg Tecfidera® p.o. twice daily, split into a morning and an evening dose. At week 2, the daily dose is further increased to 240 mg Tecfidera® p.o. in the morning and 120 mg Tecfidera® p.o. in the evening. Finally at week 3, the dose will be increased to the final daily dose of 240 mg Tecfidera® p.o. in the morning and 240 mg Tecfidera® p.o. in the evening and maintained throughout the study.
| Study group | Role | What they receive |
|---|---|---|
| Dimethyl fumarate treatment arm (A) | Active comparator | All patients will receive dimethyl fumarate (Tecfidera®) according to national recommendations (Krankheitsbezogenes Kompetenznetz Multiple Sklerose, KKNMS) from week 0 to week 24 (EOS-1) in the core study. Receives: Drug: Dimethyl fumarate |
| Healthy subject arm (B) | No intervention | Healthy subjects will not receive any treatment for RRMS during the study. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Expression of lymphocyte phenotypic surface markers in dimethyl fumarate (Tecfidera®)-treated patients with relapsing-remitting multiple sclerosis.
Measured: 0, 8, 16 and 24 weeks after initiation of investigational treatment (week 0)
Expression of lymphocyte phenotypic surface markers in dimethyl fumarate (Tecfidera®)-treated patients with relapsing-remitting multiple sclerosis and untreated healthy subjects.
Measured: 0, 8, 16 and 24 weeks after initiation of investigational treatment (week 0)
Secondary outcomes (6)
T cell effector functions in terms of cytokine production of CD4+ and CD8+ in dimethyl fumarate (Tecfidera®)-treated patients with relapsing-remitting multiple sclerosis.
Measured: 0, 8, 16 and 24 weeks after initiation of investigational treatment (week 0)
T cell effector functions in terms of cytokine production of CD4+ and CD8+ in dimethyl fumarate (Tecfidera®)-treated patients with relapsing-remitting multiple sclerosis and untreated healthy subjects.
Measured: 0, 8, 16 and 24 weeks after initiation of investigational treatment (week 0)
Migratory capacity of immune cells (percentage of migrated cells) in dimethyl fumarate (Tecfidera®)-treated patients with relapsing-remitting multiple sclerosis.
Measured: 0 and 24 weeks after initiation of investigational treatment (week 0)
Migratory capacity of immune cells (percentage of migrated cells) in dimethyl fumarate (Tecfidera®)-treated patients with relapsing-remitting multiple sclerosis and untreated healthy subjects.
Measured: 0 and 24 weeks after initiation of investigational treatment (week 0)
Mitochondrial energy metabolism of T cells upon dimethyl fumarate (Tecfidera®)-treated patients with relapsing-remitting multiple sclerosis.
Measured: 0 and 24 weeks after initiation of investigational treatment (week 0)
Mitochondrial energy metabolism of T cells upon dimethyl fumarate (Tecfidera®)-treated patients with relapsing-remitting multiple sclerosis and untreated healthy subjects.
Measured: 0 and 24 weeks after initiation of investigational treatment (week 0)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2015 (estimated)
- Study start6 May 2015
- Primary completion24 Jan 2018
- Study completion7 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple Sclerosis, Relapsing-RemittingStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Muenster
- Sponsor type
- University, hospital or other
- Collaborators
- Biogen
- Responsible party
- Sponsor
- Investigators
- Luisa Klotz, Prof. Dr., Principal investigator, University Hospital Muenster
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02461069
- Sponsor's protocol ID
- DIMAT-MS
- Other IDs
- 2014-003481-25, U1111-1164-2476, 2014
- Acronym
- DIMAT-MS
- Status last verified
- Oct 2018
- First submitted
- 27 May 2015
- Last updated
- 11 Oct 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 24-week, Multicenter, Exploratory, Two Arm Study to Assess the Effect of Dimethyl Fumarate on Immune-Modulatory Action on T Cells in Patients With Relapsing Remitting Multiple Sclerosis (DIMAT-MS)
- ClinicalTrials.gov ID
- NCT02461069
- Acronym / sponsor ID
- DIMAT-MS / DIMAT-MS
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Keywords
- dimethyl fumarate
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 67 participants (actual)
- Lead sponsor
- University Hospital MuensterUniversity, hospital or other
- Collaborators
- Biogen
- Study start
- 6 May 2015 (actual)
- Primary completion
- 24 Jan 2018 (actual)
- Study completion
- 7 May 2018 (actual)
- First posted
- 3 Jun 2015 (estimated)
- 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.
This is an exploratory study, which allows analysis of multiple immune parameters derived from peripheral blood mononuclear cells (PBMCs) from patients with relapsing remitting multiple sclerosis before and during immune-modulatory treatment with dimethyl fumarate in comparison to PBMCs from healthy subjects.
Detailed description
The purpose of the trial is to shed more light on the mechanisms of action of dimethyl fumarate in patients with relapsing remitting multiple sclerosis. More specifically the influence of dimethyl fumarate on peripheral immune cells will be addressed to evaluate changes in cytokine production by the distinct T cell subsets and the differentiation capacity of naïve T cells. Furthermore, the impact of dimethyl fumarate treatment on the migratory capacity of T cells as well as the evaluation of changes in the suppressive capacity of regulatory T cells will be evaluated. To put the obtained results into context, response data of dimethyl fumarate-treated patients will be compared with data from healthy subjects.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dimethyl fumarate treatment arm (A) | Active comparator | Drug: Dimethyl fumarateAll patients will receive dimethyl fumarate (Tecfidera®) according to national recommendations (Krankheitsbezogenes Kompetenznetz Multiple Sklerose, KKNMS) from week 0 to week 24 (EOS-1) in the core study. |
| Healthy subject arm (B) | No intervention | –Healthy subjects will not receive any treatment for RRMS during the study. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (14 listed)
- H-1. Written informed consent must be obtained before any assessment is performed.
- H-2. Male and female subjects aged 18 - 60 years.
- H-3. No history of multiple sclerosis or clinically isolated syndrome.
- H-4. No history of other autoimmune diseases, which has been treated systemically with corticosteroids, immunomodulators or immunosuppressive drugs at any time point.
- MS-1. Written informed consent must be obtained before any assessment is performed.
Key exclusion criteria (25 listed)
- MS-1. Known hypersensitivity to dimethyl fumarate or any ingredients of Tecfidera® (microcrystalline cellulose; croscarmellose-sodium; talcum; high dispersion, hydrophobic silicon dioxide; magnesiumstearate (Ph. Eur.); triethylcitrate; methacrylic acid-methacrylate copolymer (1:1) (Ph. Eur.); methacrylic acid-ethylacrylate copolymer (1:1)-dispersion 30% (Ph. Eur.), simeticon, sodiumdodecylsulfate, polysorbate 80, gelantine, titanium oxide (E171), brilliant blue (E133), hydrated Iron(III)-oxide hydroxide (E172), shellac, potassium hydroxide.
- MS-2. A MS-relapse within 30 days prior to screening.
- MS-3. Known history of active tuberculosis or active tuberculosis determined by a positive QuantiFERON® TB Gold test (i.e. a negative test result has to be provided at screening unless a negative test result exists from the last 3 months prior to screening).
- MS-4. Moderate to severe impairment of liver function or persisting elevations > 2 x ULN (confirmed by retest) of serum glutamic pyruvic transaminase/ alanine aminotransferase (SGPT/ALT) or serum glutamic oxaloacetic transaminase/aspartate aminotransferase (SGOT/AST), except patients with confirmed Gilbert´s syndrome (Meulengracht´s disease).
- MS-5. Moderate to severe impairment of renal function, as shown by serum creatinine > 133 μmol/L (or > 1.5 mg/dL).
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 |
|---|---|---|
| Dimethyl fumarateAlso: Tecfidera®Dimethyl fumarate (Tecfidera®) treatment is initiated by daily administration of 120 mg Tecfidera® p.o. in the morning in week 0. At week 1, the dose is increased to 120 mg Tecfidera® p.o. twice daily, split into a morning and an evening dose. At week 2, the daily dose is further increased to 240 mg Tecfidera® p.o. in the morning and 120 mg Tecfidera® p.o. in the evening. Finally at week 3, the dose will be increased to the final daily dose of 240 mg Tecfidera® p.o. in the morning and 240 mg Tecfidera® p.o. in the evening and maintained throughout the study. | Drug | Dimethyl fumarate treatment arm (A) |
Primary outcome
Expression of lymphocyte phenotypic surface markers in dimethyl fumarate (Tecfidera®)-treated patients with relapsing-remitting multiple sclerosis.
Time frame: 0, 8, 16 and 24 weeks after initiation of investigational treatment (week 0)
Expression of lymphocyte phenotypic surface markers in dimethyl fumarate (Tecfidera®)-treated patients with relapsing-remitting multiple sclerosis and untreated healthy subjects.
Time frame: 0, 8, 16 and 24 weeks after initiation of investigational treatment (week 0)
6 secondary outcomes
T cell effector functions in terms of cytokine production of CD4+ and CD8+ in dimethyl fumarate (Tecfidera®)-treated patients with relapsing-remitting multiple sclerosis.
Time frame: 0, 8, 16 and 24 weeks after initiation of investigational treatment (week 0)
T cell effector functions in terms of cytokine production of CD4+ and CD8+ in dimethyl fumarate (Tecfidera®)-treated patients with relapsing-remitting multiple sclerosis and untreated healthy subjects.
Time frame: 0, 8, 16 and 24 weeks after initiation of investigational treatment (week 0)
Migratory capacity of immune cells (percentage of migrated cells) in dimethyl fumarate (Tecfidera®)-treated patients with relapsing-remitting multiple sclerosis.
Time frame: 0 and 24 weeks after initiation of investigational treatment (week 0)
Migratory capacity of immune cells (percentage of migrated cells) in dimethyl fumarate (Tecfidera®)-treated patients with relapsing-remitting multiple sclerosis and untreated healthy subjects.
Time frame: 0 and 24 weeks after initiation of investigational treatment (week 0)
Mitochondrial energy metabolism of T cells upon dimethyl fumarate (Tecfidera®)-treated patients with relapsing-remitting multiple sclerosis.
Time frame: 0 and 24 weeks after initiation of investigational treatment (week 0)
Mitochondrial energy metabolism of T cells upon dimethyl fumarate (Tecfidera®)-treated patients with relapsing-remitting multiple sclerosis and untreated healthy subjects.
Time frame: 0 and 24 weeks after initiation of investigational treatment (week 0)
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 11 Oct 2018.
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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.
Luisa Klotz, Prof. Dr. principal investigator
University Hospital Muenster
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dimethyl fumarate in people with Multiple Sclerosis, Relapsing-Remitting, run by University Hospital Muenster at 6 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 14 inclusion and 25 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 11 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Expression of lymphocyte phenotypic surface markers in dimethyl fumarate (Tecfidera®)-treated patients with relapsing-remitting multiple sclerosis. (time frame: 0, 8, 16 and 24 weeks after initiation of investigational treatment (week 0)). The study lists 2 primary outcomes in all. 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 11 Oct 2018.