Multiple SclerosisPhase 4NCT02675413
Mechanisms of Action of Dimethyl Fumarate (Tecfidera) in Relapsing MS
A Phase 4 study testing Dimethyl Fumarate in people with Multiple Sclerosis and Multiple Sclerosis, Relapsing-Remitting, run by Washington University School of Medicine at 2 sites in United States.
Trial summary
This is a prospective study that will explore the mechanisms of efficacy of dimethyl fumarate (DMF) treatment in multiple sclerosis (MS). Investigators will enroll relapsing MS patients who are beginning therapy with DMF into a one-year longitudinal study in which blood and spinal fluid analyses, imaging and clinical… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting
- What is being tested?
- Dimethyl Fumarate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 2 sitesUnited States
- Study dates
- Apr 2016to Apr 2016
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of Relapsing MS (2010 McDonald Criteria)
- Age greater than or equal to 18.
- Starting treatment with dimethyl fumarate (DMF). Enrolled patients will be either naive to disease modifying therapy (DMT) or will be enrolled after a greater than or equal to 30 days from last dose of prior DMT. If enrolled patients cannot tolerate DMF, the will be replaced by another subject. All subjects will serve as their own control.
Who cannot join
- Women of Childbearing Potential who are pregnant, breastfeeding, or planning to become pregnant or breastfeed for the duration of the study.
- Chronic diseases that will have effects on the laboratory, clinical and imaging parameters we will study: Insulin-dependent diabetes mellitus, stroke, Alzheimer's disease, auto-immune disorders such as rheumatoid arthritis, lupus, neuromyelitis optica, mixed connective disease, or sjogren's disease.
- Any prior treatment with mitoxantrone or alemtuzumab.
- Those undergoing DMT within the past 12 months with rituximab or daclizumab.
- Patients treated with chronic (monthly) systemic steroids.
- Patients treated with steroids (intravenous, intramuscular, oral or ACTH) with the intent to treat MS within 30 days of the baseline visit.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Swedish Neuroscience Institute
Seattle, Washington, 98122
Washington University (John L. Trotter MS Center)
St Louis, Missouri, 63110
About this study
Official title: Mechanisms of Action of Dimethyl Fumarate in Relapsing MS
This is a prospective study that will explore the mechanisms of efficacy of dimethyl fumarate (DMF) treatment in multiple sclerosis (MS). Investigators will enroll relapsing MS patients who are beginning therapy with DMF into a one-year longitudinal study in which blood and spinal fluid analyses, imaging and clinical studies will be performed to identify and measure changes associated with DMF therapy.
Read the detailed description
The emergence of Dimethyl Fumarate (DMF) as an oral agent for the treatment of relapsing multiple sclerosis (MS) has the potential to reduce the burden of neurologic disability while minimizing side effects and risks associated with more established therapies. However, at present there is a need for further understanding of the mechanisms of action for DMF. That is, it is not yet known whether the benefits observed in MS patients treated with DMF are due primarily to immunologic and anti-inflammatory effects or neuroprotective effects, or both. The main site(s) of DMF actions, whether in the CNS and/or the periphery, is also not known.
Dimethyl fumarate is believed to act centrally by enhancing the nuclear factor erythroid 2 related factor 2 (Nrf2) transcriptional pathway, which regulates enzymes to counter act oxidative stress . DMF may enhance the Nrf2 transcriptional pathway within the CNS, but this is unproven. DMF is also anti-inflammatory, and is known to inhibit NFB translocation to the nucleus [and chemokine-induced monocyte chemotaxis. Inhibition of NFB could occur systemically, or within the CNS, or both. Therefore, investigators intend to investigate antioxidant and immunologic changes within the central nervous system (CNS) and blood in relation to DMF therapy.
- Being tested
- Dimethyl Fumarate
- Keywords
- Cerebral Spinal Fluid, Dimethyl Fumarate, Tecfidera, Multiple Sclerosis, Relapsing MS, RRMS, Mechanism of Action
- Medical subject headings
- Multiple Sclerosis, 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
Open-label
| Study group | Role | What they receive |
|---|---|---|
| Dimethyl Fumarate | Experimental | Open label dimethyl fumarate (Tecfidera) at the US approved dose of 120mg BID for 7 days and then 240mg BID thereafter for 12 months. Receives: Drug: Dimethyl Fumarate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean differences in Indicators of Oxidative stress (Nitrate, nitrite (um/L), Glutathione (uM), and F2-isoprostanes (pg/ml)) in blood and CSF at baseline and 12 months
Mean difference in Nitrate, nitrite (um/L), Glutathione (uM), and F2-isoprostanes (pg/ml)
Measured: 24 months
Mean differences in markers of axonal damage to assess whether DMF protects against neurodegeneration at baseline and 12 months
mean differences in neurofilament heavy and light chains, and tau protein in blood and spinal fluid
Measured: 24 months
Mean differences in MS-relevant cytokines, chemokines and osteopontin to examine the immunologic consequences of DMF therapy during autoimmune CNS inflammation.
Mean differences in CXCL13 (pg/ml), CCL2 (pg/ml), TNF (pg/ml), IFNg (pg/ml),IL-17 (pg/ml), Osteopontin (pg/ml)
Measured: 24 months
Mean differences in the phenotype and activation status of adaptive and innate immune cells in the CSF and peripheral circulation at baseline and 12 months.
Mean differences in CD4 (% and cells/uL) , CD8 (% and cells/uL), CD117 (% and cells/uL), HLA-DR (% and cells/uL), CD123 (% and cells/uL), CD19 (% and cells/uL),CD14, monocytes (% and cells/uL), CD11c (% and cells/uL), BDCA2 (% and cells/uL), CD56 and CD16, NK cells (% and cells/uL), CD138, plasmablasts (% and cells/uL)
Measured: 24 months
Secondary outcomes (1)
Correlation of Biomarkers with Imaging and Clinical Outcome Measures
A secondary goal is to correlate the biomarkers listed in the primary objectives with the number of gadolinium enhancing, T2W and T1W lesions seen at baseline and 12 months.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2016 (estimated)
- Study startApr 2016
- Primary completionApr 2016
- Study completionApr 2016
Why it stopped: Principal Investigator decided to withdraw.
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 Washington University School of MedicineThe 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 4
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Biogen
- Responsible party
- Sponsor
- Investigators
- Anne Cross, MD, Principal investigator, Washington University School of MedicineLaura Piccio, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02675413
- Sponsor's protocol ID
- 201511112
- Status last verified
- Jul 2016
- First submitted
- 11 Jan 2016
- Last updated
- 20 Jul 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided: Unclear what results may be available for sharing. We plan to publish group analysis.
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms of Action of Dimethyl Fumarate in Relapsing MS
- ClinicalTrials.gov ID
- NCT02675413
- Acronym / sponsor ID
- 201511112
- Keywords
- Cerebral Spinal Fluid, Dimethyl Fumarate, Tecfidera, Multiple Sclerosis, Relapsing MS, RRMS, Mechanism of Action
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Principal Investigator decided to withdraw.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- Biogen
- Study start
- Apr 2016
- Primary completion
- Apr 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 5 Feb 2016 (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 a prospective study that will explore the mechanisms of efficacy of dimethyl fumarate (DMF) treatment in multiple sclerosis (MS). Investigators will enroll relapsing MS patients who are beginning therapy with DMF into a one-year longitudinal study in which blood and spinal fluid analyses, imaging and clinical studies will be performed to identify and measure changes associated with DMF therapy.
Detailed description
The emergence of Dimethyl Fumarate (DMF) as an oral agent for the treatment of relapsing multiple sclerosis (MS) has the potential to reduce the burden of neurologic disability while minimizing side effects and risks associated with more established therapies. However, at present there is a need for further understanding of the mechanisms of action for DMF. That is, it is not yet known whether the benefits observed in MS patients treated with DMF are due primarily to immunologic and anti-inflammatory effects or neuroprotective effects, or both. The main site(s) of DMF actions, whether in the CNS and/or the periphery, is also not known.
Dimethyl fumarate is believed to act centrally by enhancing the nuclear factor erythroid 2 related factor 2 (Nrf2) transcriptional pathway, which regulates enzymes to counter act oxidative stress . DMF may enhance the Nrf2 transcriptional pathway within the CNS, but this is unproven. DMF is also anti-inflammatory, and is known to inhibit NFB translocation to the nucleus [and chemokine-induced monocyte chemotaxis. Inhibition of NFB could occur systemically, or within the CNS, or both. Therefore, investigators intend to investigate antioxidant and immunologic changes within the central nervous system (CNS) and blood in relation to DMF therapy.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dimethyl Fumarate | Experimental | Drug: Dimethyl FumarateOpen label dimethyl fumarate (Tecfidera) at the US approved dose of 120mg BID for 7 days and then 240mg BID thereafter for 12 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Diagnosis of Relapsing MS (2010 McDonald Criteria)
- Age greater than or equal to 18.
- Starting treatment with dimethyl fumarate (DMF). Enrolled patients will be either naive to disease modifying therapy (DMT) or will be enrolled after a greater than or equal to 30 days from last dose of prior DMT. If enrolled patients cannot tolerate DMF, the will be replaced by another subject. All subjects will serve as their own control.
Key exclusion criteria (6 listed)
- Women of Childbearing Potential who are pregnant, breastfeeding, or planning to become pregnant or breastfeed for the duration of the study.
- Chronic diseases that will have effects on the laboratory, clinical and imaging parameters we will study: Insulin-dependent diabetes mellitus, stroke, Alzheimer's disease, auto-immune disorders such as rheumatoid arthritis, lupus, neuromyelitis optica, mixed connective disease, or sjogren's disease.
- Any prior treatment with mitoxantrone or alemtuzumab.
- Those undergoing DMT within the past 12 months with rituximab or daclizumab.
- Patients treated with chronic (monthly) systemic steroids.
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: TecfideraOpen-label | Drug | Dimethyl Fumarate |
Primary outcome
Mean differences in Indicators of Oxidative stress (Nitrate, nitrite (um/L), Glutathione (uM), and F2-isoprostanes (pg/ml)) in blood and CSF at baseline and 12 months
Time frame: 24 months
Mean difference in Nitrate, nitrite (um/L), Glutathione (uM), and F2-isoprostanes (pg/ml)
Mean differences in markers of axonal damage to assess whether DMF protects against neurodegeneration at baseline and 12 months
Time frame: 24 months
mean differences in neurofilament heavy and light chains, and tau protein in blood and spinal fluid
Mean differences in MS-relevant cytokines, chemokines and osteopontin to examine the immunologic consequences of DMF therapy during autoimmune CNS inflammation.
Time frame: 24 months
Mean differences in CXCL13 (pg/ml), CCL2 (pg/ml), TNF (pg/ml), IFNg (pg/ml),IL-17 (pg/ml), Osteopontin (pg/ml)
Mean differences in the phenotype and activation status of adaptive and innate immune cells in the CSF and peripheral circulation at baseline and 12 months.
Time frame: 24 months
Mean differences in CD4 (% and cells/uL) , CD8 (% and cells/uL), CD117 (% and cells/uL), HLA-DR (% and cells/uL), CD123 (% and cells/uL), CD19 (% and cells/uL),CD14, monocytes (% and cells/uL), CD11c (% and cells/uL), BDCA2 (% and cells/uL), CD56 and CD16, NK cells (% and cells/uL), CD138, plasmablasts (% and cells/uL)
1 secondary outcome
Correlation of Biomarkers with Imaging and Clinical Outcome Measures
Time frame: 24 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2016.
- Individual participant dataSharing planned: Undecided. Unclear what results may be available for sharing. We plan to publish group analysis.
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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.
Anne Cross, MD principal investigator
Washington University School of Medicine
Laura Piccio, MD principal investigator
Washington University School of Medicine
2 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 and Multiple Sclerosis, Relapsing-Remitting, run by Washington University School of Medicine at 2 sites in United States.
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 3 inclusion and 6 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: withdrawn, as of the sponsor's last update on 20 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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 was withdrawn before enrolling participants, so there are no results.
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?
Mean differences in Indicators of Oxidative stress (Nitrate, nitrite (um/L), Glutathione (uM), and F2-isoprostanes (pg/ml)) in blood and CSF at baseline and 12 months (time frame: 24 months). The study lists 4 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 20 Jul 2016.