Final report: A double-blind, randomised, placebo-controlled pilot trial of efficacy and safety of ibudilast, a potential glial attenuator, in chronic migraine.

Published in the Journal of Pain Research, Volume 9, October 2016.

Summary

Why some patients progress from episodic migraine (having clear periods between attacks) to chronic migraine (having headache most of the time) is unknown. More importantly, there aren’t many proven treatments that can reverse this process.

In recent years, studies in animals have shown that the immune cells in the brain (glia) may be responsible for the continuation of chronic pain.  It hasn’t been possible to explore whether this is relevant in migraine in animals as there wasn’t a suitable animal model. Our hypothesis here was that glial cells are overactive in chronic migraine, causing worsening of pain, and that this could be reversed by ibudilast, a drug that has been shown to reduce glial activity in animals.

Ibudilast is a licensed drug with a good safety record usually used for treating asthma.  Our previous studies have shown that blood levels of the drug that were effective in animal models of pain could be achieved in humans with good tolerability.

Our study was a randomized, placebo-controlled study in which chronic migraine patients took medication for two eight week blocks with a four-week drug-free gap in the middle. In one block patients took ibudilast 40 mg twice daily, and in the other block they took matching capsules which contained no active drug (placebo).  Patients recorded their headache severity and duration daily.

The results showed that there was no treatment benefit with ibudilast, and worsening migraine was reported by more patients on the drug than on placebo.

Hypothesis vs. Findings

Our hypothesis was that there would be fewer migraine days when patients received ibudilast compared to placebo. However, we found that there was no trend for improvement and even a slight trend for increasing migraine with ibudilast.

Unanswered questions

Although this study showed that ibudilast was not a promising treatment for migraine, the underlying question as to whether immune cell activation in the brain is involved in migraine chronicity is still unanswered. At the time our trial was designed, there was no way of measuring glial activity in the human brain. However, in 2015 a study was published showing increased glial activity in patients with chronic low back pain. The method used there would be suitable for studying migraine patients to determine whether immune cell activity was increased, and if so, whether it would be a potentially suitable target for new treatments.

What this research means to you.

While ibudilast is not a useful treatment for reversing chronic migraine, the search for new treatment targets must continue.