NCT02739542

Brief Summary

The purpose of this investigation is to systematically study the efficacy of Tecfidera in those individuals who possess incidental white matter anomalies within the brain following a MRI study that is performed for a reason other than for the evaluation of MS (multiple sclerosis).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
87

participants targeted

Target at P50-P75 for phase_4

Timeline
Completed

Started Mar 2016

Longer than P75 for phase_4

Geographic Reach
1 country

11 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 16, 2016

Completed
3 days until next milestone

Study Start

First participant enrolled

March 19, 2016

Completed
27 days until next milestone

First Posted

Study publicly available on registry

April 15, 2016

Completed
5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 31, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 31, 2021

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

May 11, 2022

Completed
Last Updated

May 11, 2022

Status Verified

April 1, 2022

Enrollment Period

5 years

First QC Date

March 16, 2016

Results QC Date

February 28, 2022

Last Update Submit

April 13, 2022

Conditions

Multiple Sclerosis (MS)

Keywords

Radiologically Isolated Syndrome (RIS)

Outcome Measures

Primary Outcomes (1)

  • The Time From Randomization to the First Demyelinating Event (Acute or Development of an Initial Symptom Resulting in a Progressive Clinical Course)

    The primary outcome measure for this trial is the time to the first acute or progressive neurological event resulting from CNS demyelination from randomization into the trial.

    96 weeks

Secondary Outcomes (6)

  • Change in Lesion Volume on T2-weighted MRI

    Baseline, 96 weeks

  • Number of Newly Enlarging T2 Lesions

    96 weeks

  • Number of New T2 Lesions

    96 weeks

  • Newly Enlarging T2 Lesions and New T2 Lesions Combined

    96 weeks

  • Number of Contrast Enhancing Lesions

    96 weeks

  • +1 more secondary outcomes

Study Arms (2)

Tecfidera

ACTIVE COMPARATOR

Tecfidera (120mg by mouth twice daily for 7 days with dose escalation to 240mg by mouth twice daily)

Drug: Tecfidera

Placebo

PLACEBO COMPARATOR

Placebo by mouth twice daily.

Drug: Placebo

Interventions

TecfideraDRUG

Blinded drug wallets will be dispensed during routine study appointments in 3 month supply, so that compliance can be reconciled at follow up visits and telephone consultations, and recorded in accountability logs.

Also known as: Dimethyl fumarate
Tecfidera
PlaceboDRUG

Blinded drug wallets will be dispensed during routine study appointments in 3 month supply, so that compliance can be reconciled at follow up visits and telephone consultations, and recorded in accountability logs.

Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Males and females meeting 2009 RIS criteria
  • Identified RIS cases with the initial MRI demonstrating anomalies suggestive of demyelinating disease dated \> 2009
  • Incidental anomalies identified on MRI of the brain or spinal cord with the primary reason for the acquired MRI resulting from an evaluation of a process other than MS
  • CNS white matter anomalies meeting the following MRI criteria:
  • Ovoid, well-circumscribed, and homogeneous foci with or without involvement of the corpus callosum
  • T2-hyperintensities measuring \> 3mm2 and fulfilling 3 of 4 Barkhof-Tintoré criteria for dissemination in space
  • CNS anomalies not consistent with a vascular pattern
  • Qualitative determination that CNS anomalies have a characteristic appearance of demyelinating lesions
  • MRI anomalies do not account for clinically apparent neurological impairments in patients

You may not qualify if:

  • Women who are pregnant or nursing
  • Incomplete medical history or radiological data
  • History of remitting clinical symptoms consistent with multiple sclerosis lasting \> 24 hours prior to CNS imaging revealing anomalies suggestive of MS
  • History of paroxysmal symptoms associated with MS (i.e. Lhermitte's or Uhthoff's phenomena)
  • CNS MRI anomalies are better accounted for by another disease process
  • The subject is unwilling or unable to comply with the requirements of the study protocol
  • Exposure to a disease modifying therapy for MS/RIS within the past 3 months
  • Exposure to high-dose glucocorticosteroid treatment within the past 30 days
  • Participation in other clinical trials involving treatment with a disease-modifying agent

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

Keck School of Medicine - USC - Department of Neurology

Los Angeles, California, 90089, United States

Location

Johns Hopkins University - Neurology

Baltimore, Maryland, 21287, United States

Location

Mayo Clinic Department of Neurology

Rochester, Minnesota, 55905, United States

Location

Washington University Department of Neurology

St Louis, Missouri, 63110, United States

Location

Cleveland Clinic - Lou Ruvo Center for Brain Health

Las Vegas, Nevada, 89106, United States

Location

MS Clinical Care and Research Center, Dept of Neurology, Columbia University

New York, New York, 10032, United States

Location

Oklahoma Medical Research Foundation, MS Center of Excellence

Oklahoma City, Oklahoma, 73104, United States

Location

MS Treatment Center of Dallas

Dallas, Texas, 75246, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390-8806, United States

Location

Swedish Medical Center

Seattle, Washington, 98122, United States

Location

MultiCare Institute for Research and Innovation

Tacoma, Washington, 98405, United States

Location

Related Publications (12)

  • Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, Lublin FD, Metz LM, McFarland HF, O'Connor PW, Sandberg-Wollheim M, Thompson AJ, Weinshenker BG, Wolinsky JS. Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria". Ann Neurol. 2005 Dec;58(6):840-6. doi: 10.1002/ana.20703.

    PMID: 16283615BACKGROUND

  • Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin FD, Montalban X, O'Connor P, Sandberg-Wollheim M, Thompson AJ, Waubant E, Weinshenker B, Wolinsky JS. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011 Feb;69(2):292-302. doi: 10.1002/ana.22366.

    PMID: 21387374BACKGROUND

  • Lebrun C, Bensa C, Debouverie M, De Seze J, Wiertlievski S, Brochet B, Clavelou P, Brassat D, Labauge P, Roullet E; CFSEP. Unexpected multiple sclerosis: follow-up of 30 patients with magnetic resonance imaging and clinical conversion profile. J Neurol Neurosurg Psychiatry. 2008 Feb;79(2):195-8. doi: 10.1136/jnnp.2006.108274.

    PMID: 18202208BACKGROUND

  • Siva A, Saip S, Altintas A, Jacob A, Keegan BM, Kantarci OH. Multiple sclerosis risk in radiologically uncovered asymptomatic possible inflammatory-demyelinating disease. Mult Scler. 2009 Aug;15(8):918-27. doi: 10.1177/1352458509106214.

    PMID: 19667020BACKGROUND

  • Lebrun C, Blanc F, Brassat D, Zephir H, de Seze J; CFSEP. Cognitive function in radiologically isolated syndrome. Mult Scler. 2010 Aug;16(8):919-25. doi: 10.1177/1352458510375707. Epub 2010 Jul 7.

    PMID: 20610492BACKGROUND

  • De Stefano N, Stromillo ML, Rossi F, Battaglini M, Giorgio A, Portaccio E, Hakiki B, Malentacchi G, Gasperini C, Santangelo M, Bartolozzi ML, Sormani MP, Federico A, Amato MP. Improving the characterization of radiologically isolated syndrome suggestive of multiple sclerosis. PLoS One. 2011 Apr 29;6(4):e19452. doi: 10.1371/journal.pone.0019452.

    PMID: 21559385BACKGROUND

  • Gabelic T, Radmilovic M, Posavec V, Skvorc A, Boskovic M, Adamec I, Milivojevic I, Barun B, Habek M. Differences in oligoclonal bands and visual evoked potentials in patients with radiologically and clinically isolated syndrome. Acta Neurol Belg. 2013 Mar;113(1):13-7. doi: 10.1007/s13760-012-0106-1. Epub 2012 Jun 28.

    PMID: 22740024BACKGROUND

  • Giorgio A, Stromillo ML, Rossi F, Battaglini M, Hakiki B, Portaccio E, Federico A, Amato MP, De Stefano N. Cortical lesions in radiologically isolated syndrome. Neurology. 2011 Nov 22;77(21):1896-9. doi: 10.1212/WNL.0b013e318238ee9b. Epub 2011 Nov 9.

    PMID: 22076541BACKGROUND

  • Lebrun C, Le Page E, Kantarci O, Siva A, Pelletier D, Okuda DT; Club Francophone de Sclerose en Plaques (CFSEP); Radiologically Isolated Syndrome Consortium (RISC) Group. Impact of pregnancy on conversion to clinically isolated syndrome in a radiologically isolated syndrome cohort. Mult Scler. 2012 Sep;18(9):1297-302. doi: 10.1177/1352458511435931. Epub 2012 Feb 2.

    PMID: 22300971BACKGROUND

  • Okuda DT, Mowry EM, Cree BA, Crabtree EC, Goodin DS, Waubant E, Pelletier D. Asymptomatic spinal cord lesions predict disease progression in radiologically isolated syndrome. Neurology. 2011 Feb 22;76(8):686-92. doi: 10.1212/WNL.0b013e31820d8b1d. Epub 2011 Jan 26.

    PMID: 21270417BACKGROUND

  • Okuda DT, Mowry EM, Beheshtian A, Waubant E, Baranzini SE, Goodin DS, Hauser SL, Pelletier D. Incidental MRI anomalies suggestive of multiple sclerosis: the radiologically isolated syndrome. Neurology. 2009 Mar 3;72(9):800-5. doi: 10.1212/01.wnl.0000335764.14513.1a. Epub 2008 Dec 10.

    PMID: 19073949RESULT

  • Okuda DT, Kantarci O, Lebrun-Frenay C, Sormani MP, Azevedo CJ, Bovis F, Hua LH, Amezcua L, Mowry EM, Hotermans C, Mendoza J, Walsh JS, von Hehn C, Vargas WS, Donlon S, Naismith RT, Okai A, Pardo G, Repovic P, Stuve O, Siva A, Pelletier D. Dimethyl Fumarate Delays Multiple Sclerosis in Radiologically Isolated Syndrome. Ann Neurol. 2023 Mar;93(3):604-614. doi: 10.1002/ana.26555. Epub 2022 Dec 10.

    PMID: 36401339DERIVED

Related Links

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Dimethyl Fumarate

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNSAutoimmune Diseases of the Nervous SystemNervous System DiseasesDemyelinating DiseasesAutoimmune DiseasesImmune System Diseases

Intervention Hierarchy (Ancestors)

FumaratesDicarboxylic AcidsAcids, AcyclicCarboxylic AcidsOrganic Chemicals

Results Point of Contact

Title
Darin T. Okuda, M.D.
Organization
UT Southwestern Medical Center
darin.okuda@utsouthwestern.edu
214-645-8800

Study Officials

  • Darin T Okuda, MD

    University of Texas Southwestern Medical Center

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
PROFESSOR

Study Record Dates

First Submitted

March 16, 2016

First Posted

April 15, 2016

Study Start

March 19, 2016

Primary Completion

March 31, 2021

Study Completion

March 31, 2021

Last Updated

May 11, 2022

Results First Posted

May 11, 2022

Record last verified: 2022-04

Data Sharing

IPD Sharing
Will not share

Locations

US(11)