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

NCT02675413 | Withdrawn Phase 4

• 1 other identifier: 201511112
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

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.

Conditions

Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting

Keywords

Cerebral Spinal Fluid; Dimethyl Fumarate; Tecfidera; Multiple Sclerosis; Relapsing MS; RRMS; Mechanism of Action

Outcome Measures

Primary Outcomes (4)

• 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)

  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

  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)

  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)

  24 months

Secondary Outcomes (1)

• Correlation of Biomarkers with Imaging and Clinical Outcome Measures

  24 months

Study Arms (1)

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.

Drug: Dimethyl Fumarate

Interventions

Dimethyl Fumarate DRUG

Open-label

Also known as: Tecfidera

Dimethyl Fumarate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Biogen: collaborator

Study Sites (2)

Washington University (John L. Trotter MS Center)

St Louis, Missouri, 63110, United States

Location

Swedish Neuroscience Institute

Seattle, Washington, 98122, United States

Location

MeSH Terms

Conditions

Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting

Interventions

Dimethyl Fumarate

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Fumarates; Dicarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Anne Cross, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

• Laura Piccio, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2016
• First Posted: February 5, 2016
• Study Start: April 1, 2016
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: July 20, 2016

Record last verified: 2016-07

Locations

US (2)