Investigation of the Effect of Dimethyl Fumarate on T Cells in Patients With Relapsing Remitting Multiple Sclerosis (DIMAT-MS)

October 10, 2018 updated by: University Hospital Muenster

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
67

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Bonn, Germany, 53111
        • Neurologisches Studienzentrum Dr. Schmidt/Dr. Neudecker/ Dr. Viehbahn/Dr. Kronenberger
      • Frankfurt am Main, Germany, 60313
        • Neurologische Gemeinschaftspraxis im Bienenkorbhaus
      • Heidelberg, Germany, 69120
        • Neurologische Univ.-Klinik
      • Mainz, Germany, 55131
        • Klinik und Poliklinik für Neurologie, Universitätsklinikum Mainz
      • Muenster, Germany, 48149
        • University Hospital Muenster, Department of Neurology
      • Osnabrück, Germany, 49076
        • MVZ-Neurologie Klinikum Osnabrück GmbH

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

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:

  • 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.

Exclusion Criteria:

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).
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Dimethyl fumarate treatment arm (A)
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.
Drug: Dimethyl fumarate
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.
Other Names:
  • Tecfidera®
No Intervention: Healthy subject arm (B)
Healthy subjects will not receive any treatment for RRMS during the study.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
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)
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)
0, 8, 16 and 24 weeks after initiation of investigational treatment (week 0)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
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)
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)
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)
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)
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)
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)
0 and 24 weeks after initiation of investigational treatment (week 0)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital Muenster

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Biogen

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Luisa Klotz, Prof. Dr., University hospital Muenster

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 6, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 24, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 7, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 27, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 29, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 3, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 11, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 10, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • DIMAT-MS
  • 2014-003481-25 (EudraCT Number)
  • U1111-1164-2476 (Other Identifier: Universal Trial Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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