Mechanisms of Action of Dimethyl Fumarate (Tecfidera) in Relapsing MS

NCT ID: NCT02675413

Last Updated: 2016-07-20

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE4
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-04-30
• Study Completion Date: 2016-04-30

Brief 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 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.

Conditions

Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Dimethyl Fumarate

Open label dimethyl fumarate (Tecfidera) at the US approved dose of 120mg BID for 7 days and then 240mg BID thereafter for 12 months.

Group Type: EXPERIMENTAL

Dimethyl Fumarate

Intervention Type: DRUG

Open-label

Interventions

Dimethyl Fumarate

Open-label

Intervention Type: DRUG

Other Intervention Names

Tecfidera

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Biogen

INDUSTRY

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anne Cross, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Laura Piccio, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University (John L. Trotter MS Center)

St Louis, Missouri, United States

Swedish Neuroscience Institute

Seattle, Washington, United States

Countries

United States

Other Identifiers

201511112

Identifier Type: -

Identifier Source: org_study_id