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Clinical Trial
. 2016 Sep:50:166-77.
doi: 10.1016/j.cct.2016.08.009. Epub 2016 Aug 10.

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

Robert J Fox  1 , Christopher S Coffey  2 , Merit E Cudkowicz  3 , Trevis Gleason  4 , Andrew Goodman  5 , Eric C Klawiter  6 , Kazuko Matsuda  7 , Michelle McGovern  3 , Robin Conwit  8 , Robert Naismith  9 , Akshata Ashokkumar  2 , Robert Bermel  10 , Dixie Ecklund  2 , Maxine Koepp  2 , Jeffrey Long  2 , Sneha Natarajan  10 , Srividya Ramachandran  10 , Thomai Skaramagas  10 , Brenda Thornell  3 , Jon Yankey  2 , Mark Agius  11 , Khurram Bashir  12 , Bruce Cohen  13 , Patricia Coyle  14 , Silvia Delgado  15 , Dana Dewitt  16 , Angela Flores  17 , Barbara Giesser  18 , Myla Goldman  19 , Burk Jubelt  20 , Neil Lava  21 , Sharon Lynch  22 , Augusto Miravalle  23 , Harold Moses  24 , Daniel Ontaneda  10 , Jai Perumal  25 , Michael Racke  26 , Pavle Repovic  27 , Claire Riley  28 , Christopher Severson  29 , Shlomo Shinnar  30 , Valerie Suski  31 , Bianca Weinstock-Gutman  32 , Vijayshree Yadav  33 , Aram Zabeti  34
Affiliations
Clinical Trial

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

Robert J Fox et al. Contemp Clin Trials. 2016 Sep.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Clinical trial; Ibudilast; Magnetic resonance imaging; Progressive multiple sclerosis.

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Figures

Figure 1
Figure 1
A schematic of events scheduled at each study visit in the SPRINT-MS trial.
Figure 2
Figure 2
Overall rate of enrollment (A) and randomization (B) in the SPRINT-MS trial.
Figure 3
Figure 3
SPRINT-MS trial flow diagram (per CONSORT specifications).
See this image and copyright information in PMC

References

    1. Cottrell DA, Kremenchutzky M, Rice GP, Hader W, Baskerville J, Ebers GC. The natural history of multiple sclerosis: a geographically based study. 6. Applications to planning and interpretation of clinical therapeutic trials in primary progressive multiple sclerosis. Brain. 1999;122:641–7. - PubMed
    1. [Accessed 17 February, 2016];International Progressive MS Alliance: Facts and Figures. 2015 at http://www.progressivemsalliance.org/progressive-ms/facts-and-figures/
    1. Barkhof F, Hulst HE, Drulovic J, Uitdehaag BM, Matsuda K, Landin R. Ibudilast in relapsing-remitting multiple sclerosis: a neuroprotectant? Neurology. 2010;74:1033–40. - PubMed
    1. Rolan P, Hutchinson M, Johnson K. Ibudilast: a review of its pharmacology, efficacy and safety in respiratory and neurological disease. Expert Opin Pharmacother. 2009;10:2897–904. - PubMed
    1. Ledeboer A, Jekich BM, Sloane EM, et al. Intrathecal interleukin-10 gene therapy attenuates paclitaxel-induced mechanical allodynia and proinflammatory cytokine expression in dorsal root ganglia in rats. Brain Behav Immun. 2007;21:686–98. - PMC - PubMed

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