title: Design, rationale, and baseline characteristics of the randomized double-blind phase II clinical trial of ibudilast in progressive multiple sclerosis.
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.
authors: Cleveland Clinic, Neurological Institute, Cleveland, OH, United States. Electronic address: foxr@ccf.org.
authors: Robert J
authors: RJ
authors: Fox
authors: Data Coordinating Center, NeuroNEXT, University of Iowa, Iowa City, IA, United States.
authors: Christopher S
authors: CS
authors: Coffey
authors: Clinical Coordinating Center, NeuroNEXT, Harvard Partners, Boston, MA, United States.
authors: Merit E
authors: ME
authors: Cudkowicz
authors: Patient Advocate, Seattle, WA, United States.
authors: Trevis
authors: T
authors: Gleason
authors: University of Rochester Medical Center, Rochester, NY, United States.
authors: Andrew
authors: A
authors: Goodman
authors: Massachusetts General Hospital, Boston, MA, United States.
authors: Eric C
authors: EC
authors: Klawiter
authors: Medicinova Inc., La Jolla, CA, United States.
authors: Kazuko
authors: K
authors: Matsuda
authors: Clinical Coordinating Center, NeuroNEXT, Harvard Partners, Boston, MA, United States.
authors: Michelle
authors: M
authors: McGovern
authors: National Institutes of Neurological Disease and Stroke, Bethesda, MD, United States.
authors: Robin
authors: R
authors: Conwit
authors: Washington University School of Medicine, St. Louis, MO, United States.
authors: Robert
authors: R
authors: Naismith
authors: Data Coordinating Center, NeuroNEXT, University of Iowa, Iowa City, IA, United States.
authors: Akshata
authors: A
authors: Ashokkumar
authors: Cleveland Clinic, Neurological Institute, Cleveland, OH, United States.
authors: Robert
authors: R
authors: Bermel
authors: Data Coordinating Center, NeuroNEXT, University of Iowa, Iowa City, IA, United States.
authors: Dixie
authors: D
authors: Ecklund
authors: Data Coordinating Center, NeuroNEXT, University of Iowa, Iowa City, IA, United States.
authors: Maxine
authors: M
authors: Koepp
authors: Data Coordinating Center, NeuroNEXT, University of Iowa, Iowa City, IA, United States.
authors: Jeffrey
authors: J
authors: Long
authors: Cleveland Clinic, Neurological Institute, Cleveland, OH, United States.
authors: Sneha
authors: S
authors: Natarajan
authors: Cleveland Clinic, Neurological Institute, Cleveland, OH, United States.
authors: Srividya
authors: S
authors: Ramachandran
authors: Cleveland Clinic, Neurological Institute, Cleveland, OH, United States.
authors: Thomai
authors: T
authors: Skaramagas
authors: Clinical Coordinating Center, NeuroNEXT, Harvard Partners, Boston, MA, United States.
authors: Brenda
authors: B
authors: Thornell
authors: Data Coordinating Center, NeuroNEXT, University of Iowa, Iowa City, IA, United States.
authors: Jon
authors: J
authors: Yankey
authors: University of California at Davis, Sacramento, CA; currently at Barrows Neurological Institute, Phoenix, AZ, United States.
authors: Mark
authors: M
authors: Agius
authors: University of Alabama at Birmingham, Birmingham, AL, United States.
authors: Khurram
authors: K
authors: Bashir
authors: Northwestern University, Chicago, IL, United States.
authors: Bruce
authors: B
authors: Cohen
authors: State University of New York, Stony Brook, NY, United States.
authors: Patricia
authors: P
authors: Coyle
authors: University of Miami School of Medicine, Miami, FL, United States.
authors: Silvia
authors: S
authors: Delgado
authors: University of Utah, Salt Lake City, UT, United States.
authors: Dana
authors: D
authors: Dewitt
authors: University of Texas Southwestern Medical Center, Dallas, TX, United States.
authors: Angela
authors: A
authors: Flores
authors: University of California at Los Angeles, Los Angeles, CA, United States.
authors: Barbara
authors: B
authors: Giesser
authors: University of Virginia at Charlottesville, Charlottesville, VA, United States.
authors: Myla
authors: M
authors: Goldman
authors: State University of New York Upstate Medical University, Syracuse, NY, United States.
authors: Burk
authors: B
authors: Jubelt
authors: Emory University, Atlanta, GA, United States.
authors: Neil
authors: N
authors: Lava
authors: University of Kansas Medical Center, Kansas City, KS, United States.
authors: Sharon
authors: S
authors: Lynch
authors: University of Colorado at Denver, Aurora, CO, United States.
authors: Augusto
authors: A
authors: Miravalle
authors: Vanderbilt University, Nashville, TN, United States.
authors: Harold
authors: H
authors: Moses
authors: Cleveland Clinic, Neurological Institute, Cleveland, OH, United States.
authors: Daniel
authors: D
authors: Ontaneda
authors: Weill Cornell Medical College, New York, NY, United States.
authors: Jai
authors: J
authors: Perumal
authors: The Ohio State University, Columbus, OH, United States.
authors: Michael
authors: M
authors: Racke
authors: Swedish Medical Center at Seattle, Seattle, WA, United States.
authors: Pavle
authors: P
authors: Repovic
authors: Columbia University Medical Center, New York, NY, United States.
authors: Claire
authors: C
authors: Riley
authors: Brigham and Women's Hospital, Brookline, MA, United States.
authors: Christopher
authors: C
authors: Severson
authors: Montefiore Medical Center, Bronx, NY, United States.
authors: Shlomo
authors: S
authors: Shinnar
authors: University of Pittsburgh Medical Center, Pittsburgh, PA, United States.
authors: Valerie
authors: V
authors: Suski
authors: State University of New York Buffalo, Buffalo, NY, United States.
authors: Bianca
authors: B
authors: Weinstock-Gutman
authors: Oregon Health and Science University, Portland, OR, United States.
authors: Vijayshree
authors: V
authors: Yadav
authors: University of Cincinnati, Cincinnati, OH, United States.
authors: Aram
authors: A
authors: Zabeti
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging; D056324:Diffusion Tensor Imaging; D018450:Disease Progression; D004311:Double-Blind Method; D006801:Humans; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000000981:diagnostic imaging / Q000188:drug therapy*; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D011788:Quality of Life; D012107:Research Design; D007212:Indolizines; D011720:Pyrazoles
chemical_list: D010726:Phosphodiesterase Inhibitors; D011725:Pyridines; C038366:ibudilast; D007212:Indolizines; D011720:Pyrazoles
keywords: Clinical trial; Ibudilast; Magnetic resonance imaging; Progressive multiple sclerosis