A double-blind, randomized, placebo-controlled pilot trial to determine the efficacy and safety of ibudilast, a potential glial attenuator, in chronic migraine

Yuen H Kwok, James E Swift, Parisa Gazerani, Paul Rolan, Yuen H Kwok, James E Swift, Parisa Gazerani, Paul Rolan

Abstract

Background: Chronic migraine (CM) is problematic, and there are few effective treatments. Recently, it has been hypothesized that glial activation may be a contributor to migraine; therefore, this study investigated whether the potential glial inhibitor, ibudilast, could attenuate CM.

Methods: The study was of double-blind, randomized, placebo-controlled, two-period crossover design. Participants were randomized to receive either ibudilast (40 mg twice daily) or placebo treatment for 8 weeks. Subsequently, the participants underwent a 4-week washout period followed by a second 8-week treatment block with the alternative treatment. CM participants completed a headache diary 4 weeks before randomization throughout both treatment periods and 4 weeks after treatment. Questionnaires assessing quality of life and cutaneous allodynia were collected on eight occasions throughout the study.

Results: A total of 33 participants were randomized, and 14 participants completed the study. Ibudilast was generally well tolerated with mild, transient adverse events, principally nausea. Eight weeks of ibudilast treatment did not reduce the frequency of moderate to severe headache or of secondary outcome measures such as headache index, intake of symptomatic medications, quality of life or change in cutaneous allodynia.

Conclusion: Using the current regimen, ibudilast does not improve migraine with CM participants.

Keywords: chronic migraine; glia; headache; ibudilast; immune system.

Conflict of interest statement

PR holds a provisional patent on the use of ibudilast in medication overuse headache. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Study overview.
Figure 2
Figure 2
Flow diagram of numbers of participants in different phases of the study.
Figure 3
Figure 3
Eight weeks of ibudilast usage did not reduce the frequency of moderate to severe headaches. Notes: CM participants recorded the frequency and intensity of headache experience in a diary throughout the course of the study. When the frequency of moderate to severe headache experience was averaged over 4-week blocks, no significant difference was found between treatments (P=0.9) but a significant difference was found between visits (*P=0.02). The values are presented as mean ± SD. Headaches were considered to be moderate if participants recorded ≥6 for “average pain intensity of headache out of 10.” Abbreviations: CM, chronic migraine; SD, standard deviation.
Figure 4
Figure 4
Ibudilast did not reduce headache index. Notes: The daily headache index, averaged over 4-week blocks detected no differences between the treatments (P=0.9); however, there was a significant reduction in the headache indices at treatment weeks 5–8 compared with treatment weeks 1–4 (**P=0.003). The average headache index was calculated by the product of headache duration and headache intensity (11-point NRS), averaged over the number of days. The values are presented as mean ± SD. Abbreviations: NRS, numerical rating scale; SD, standard deviation.
Figure 5
Figure 5
Ibudilast did not reduce the intake of symptomatic medications or the amount of oral morphine equivalent. Note: (A) There was no difference in the number of days in which symptomatic medication was taken between the treatments (P=0.6) or between visits (P=0.5). (B) There were also no treatment (P=1) or visit (P=0.2) differences in the amount of oral morphine equivalent taken between ibudilast or placebo treatments.

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