Design, rationale, and baseline characteristics of the randomized double-blind phase II clinical trial of ibudilast in progressive multiple sclerosis

Robert J Fox; Christopher S Coffey; Merit E Cudkowicz; Trevis Gleason; Andrew Goodman; Eric C Klawiter; Kazuko Matsuda; Michelle McGovern; Robin Conwit; Robert Naismith; Akshata Ashokkumar; Robert Bermel; Dixie Ecklund; Maxine Koepp; Jeffrey Long; Sneha Natarajan; Srividya Ramachandran; Thomai Skaramagas; Brenda Thornell; Jon Yankey; Mark Agius; Khurram Bashir; Bruce Cohen; Patricia Coyle; Silvia Delgado; Dana Dewitt; Angela Flores; Barbara Giesser; Myla Goldman; Burk Jubelt; Neil Lava; Sharon Lynch; Augusto Miravalle; Harold Moses; Daniel Ontaneda; Jai Perumal; Michael Racke; Pavle Repovic; Claire Riley; Christopher Severson; Shlomo Shinnar; Valerie Suski; Bianca Weinstock-Gutman; Vijayshree Yadav; Aram Zabeti

doi:10.1016/j.cct.2016.08.009

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Design, rationale, and baseline characteristics of the randomized double-blind phase II clinical trial of ibudilast in progressive multiple sclerosis

Journal article

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Design, rationale, and baseline characteristics of the randomized double-blind phase II clinical trial of ibudilast in progressive multiple sclerosis

Robert J Fox, Christopher S Coffey, Merit E Cudkowicz, Trevis Gleason, Andrew Goodman, Eric C Klawiter, Kazuko Matsuda, Michelle McGovern, Robin Conwit, Robert Naismith, …

Contemporary clinical trials, Vol.50, pp.166-177

09/2016

DOI: 10.1016/j.cct.2016.08.009

PMCID: PMC5035622

PMID: 27521810

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Abstract

Primary and secondary progressive multiple sclerosis (MS), collectively called progressive multiple sclerosis (PMS), is characterized by gradual progression of disability. The current anti-inflammatory treatments for MS have little or no efficacy in PMS in the absence of obvious active inflammation. Optimal biomarkers for phase II PMS trials is unknown. Ibudilast is an inhibitor of macrophage migration inhibitor factor and phosphodiesterases-4 and −10 and exhibits possible neuroprotective properties. The goals of SPRINT-MS study are to evaluate the safety and efficacy of ibudilast in PMS and to directly compare several imaging metrics for utility in PMS trials. SPRINT-MS is a randomized, placebo-controlled, phase II trial of ibudilast in patients with PMS. Eligible subjects were randomized 1:1 to receive either ibudilast (100mg/day) or placebo for 96weeks. Imaging is conducted every 24weeks for whole brain atrophy, magnetization transfer ratio, diffusion tensor imaging, cortical brain atrophy, and retinal nerve fiber layer thickness. Clinical outcomes include neurologic disability and patient reported quality of life. Safety assessments include laboratory testing, electrocardiography, and suicidality screening. A total of 331 subjects were enrolled, of which 255 were randomized onto active study treatment. Randomized subjects were 53.7% female and mean age 55.7 (SD 7.3) years. The last subject is projected to complete the study in May 2017. SPRINT-MS is designed to evaluate the safety and efficacy of ibudilast as a treatment for PMS while simultaneously validating five different imaging biomarkers as outcome metrics for use in future phase II proof-of-concept PMS trials.

Magnetic Resonance Imaging

Progressive multiple sclerosis

Clinical trial

Ibudilast

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Title: Subtitle: Design, rationale, and baseline characteristics of the randomized double-blind phase II clinical trial of ibudilast in progressive multiple sclerosis
Creators: Robert J Fox - Cleveland Clinic, Neurological Institute, Cleveland, OH, United States
Christopher S Coffey - Data Coordinating Center, NeuroNEXT, University of Iowa, Iowa City, IA, United States
Merit E Cudkowicz - Clinical Coordinating Center, NeuroNEXT, Harvard Partners, Boston, MA, United States
Trevis Gleason - Patient Advocate, Seattle, WA, United States
Andrew Goodman - University of Rochester Medical Center, Rochester, NY, United States
Eric C Klawiter - Massachusetts General Hospital, Boston, MA, United States
Kazuko Matsuda - Medicinova Inc., La Jolla, CA, United States
Michelle McGovern - Clinical Coordinating Center, NeuroNEXT, Harvard Partners, Boston, MA, United States
Robin Conwit - National Institutes of Neurological Disease and Stroke, Bethesda, MD, United States
Robert Naismith - Washington University School of Medicine, St. Louis, MO, United States
Akshata Ashokkumar - Data Coordinating Center, NeuroNEXT, University of Iowa, Iowa City, IA, United States
Robert Bermel - Cleveland Clinic, Neurological Institute, Cleveland, OH, United States
Dixie Ecklund - Data Coordinating Center, NeuroNEXT, University of Iowa, Iowa City, IA, United States
Maxine Koepp - Data Coordinating Center, NeuroNEXT, University of Iowa, Iowa City, IA, United States
Jeffrey Long - Data Coordinating Center, NeuroNEXT, University of Iowa, Iowa City, IA, United States
Sneha Natarajan - Cleveland Clinic, Neurological Institute, Cleveland, OH, United States
Srividya Ramachandran - Cleveland Clinic, Neurological Institute, Cleveland, OH, United States
Thomai Skaramagas - Cleveland Clinic, Neurological Institute, Cleveland, OH, United States
Brenda Thornell - Clinical Coordinating Center, NeuroNEXT, Harvard Partners, Boston, MA, United States
Jon Yankey - Data Coordinating Center, NeuroNEXT, University of Iowa, Iowa City, IA, United States
Mark Agius - University of California at Davis, Sacramento, CA; currently at Barrows Neurological Institute, Phoenix, AZ, United States
Khurram Bashir - University of Alabama at Birmingham, Birmingham, AL, United States
Bruce Cohen - Northwestern University, Chicago, IL, United States
Patricia Coyle - State University of New York, Stony Brook, NY, United States
Silvia Delgado - University of Miami School of Medicine, Miami, FL, United States
Dana Dewitt - University of Utah, Salt Lake City, UT, United States
Angela Flores - University of Texas Southwestern Medical Center, Dallas, TX, United States
Barbara Giesser - University of California at Los Angeles, Los Angeles, CA, United States
Myla Goldman - University of Virginia at Charlottesville, Charlottesville, VA, United States
Burk Jubelt - State University of New York Upstate Medical University, Syracuse, NY, United States
Neil Lava - Emory University, Atlanta, GA, United States
Sharon Lynch - University of Kansas Medical Center, Kansas City, KS, United States
Augusto Miravalle - University of Colorado at Denver, Aurora, CO, United States
Harold Moses - Vanderbilt University, Nashville, TN, United States
Daniel Ontaneda - Cleveland Clinic, Neurological Institute, Cleveland, OH, United States
Jai Perumal - Weill Cornell Medical College, New York, NY, United States
Michael Racke - The Ohio State University, Columbus, OH, United States
Pavle Repovic - Swedish Medical Center at Seattle, Seattle, WA, United States
Claire Riley - Columbia University Medical Center, New York, NY, United States
Christopher Severson - Brigham and Women's Hospital, Brookline, MA, United States
Shlomo Shinnar - Montefiore Medical Center, Bronx, NY, United States
Valerie Suski - University of Pittsburgh Medical Center, Pittsburgh, PA, United States
Bianca Weinstock-Gutman - State University of New York Buffalo, Buffalo, NY, United States
Vijayshree Yadav - Oregon Health and Science University, Portland, OR, United States
Aram Zabeti - University of Cincinnati, Cincinnati, OH, United States
Resource Type: Journal article
Publication Details: Contemporary clinical trials, Vol.50, pp.166-177
DOI: 10.1016/j.cct.2016.08.009
PMID: 27521810
PMCID: PMC5035622
NLM abbreviation: Contemp Clin Trials
ISSN: 1551-7144
eISSN: 1559-2030
Publisher: Elsevier Inc
Grant note: DOI: 10.13039/100000890, name: National Multiple Sclerosis Society, award: RG 4778-A-6, U01NS077179, U01NS077352; DOI: 10.13039/100000065, name: National Institute of Neurological Disorders and Stroke, award: U01NS082329
Language: English
Date published: 09/2016
Academic Unit: Psychiatry; Biostatistics
Record Identifier: 9983997442302771

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