Mechanisms of Action of Dimethyl Fumarate (Tecfidera) in Relapsing MS
| Status: | Withdrawn |
|---|---|
| Conditions: | Neurology, Neurology, Multiple Sclerosis |
| Therapuetic Areas: | Neurology, Other |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 7/21/2016 |
| Start Date: | April 2016 |
| End Date: | April 2016 |
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.
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.
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.
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
We found this trial at
2
sites
St. Louis, Missouri 63110
Principal Investigator: Anne H Cross, MD
Phone: 314-747-5576
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Seattle, Washington 98122
Principal Investigator: Peiqing Qian, MD
Phone: 206-320-3695
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