A Phase 4 interventional study of Dimethyl Fumarate in Multiple Sclerosis and Multiple Sclerosis, Relapsing-Remitting, sponsored by Washington University School of Medicine. Withdrawn at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2016-07-20.
Sponsored by Washington University School of Medicine · Phase 4, Interventional, and Basic science
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.
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.
3,460 studies on the registry are indexed under Multiple Sclerosis; 661 are open to participants now.
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Exclusion Criteria:
Open label dimethyl fumarate (Tecfidera) at the US approved dose of 120mg BID for 7 days and then 240mg BID thereafter for 12 months.
Drug: Dimethyl Fumarate
Open-label
Also known as: Tecfidera
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)
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: 24 months
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.
Time frame: 24 months
Plan to share: Undecided — Unclear what results may be available for sharing. We plan to publish group analysis.
No publications or documents are linked to this record.
This study is withdrawn, as verified in Jul 2016. You cannot join it, but the record below documents what was studied.
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Washington University School of Medicine