The impact of triptan and doxycycline on neuroinflammatory biomarkers in acute migraine: study protocol of a randomized controlled trial




headache, migraine, biomarkers, inflammation



Increased inflammatory cytokines and matrix metalloproteinases (MMPs) have been recently implicated in migraine. Inflammation may be a key player in the pathophysiology of migraine by altering blood-brain barrier (BBB) function. As an inflammation induced MMP, MMP-9 is involved in both BBB disruption and neuropathic pain, and is largely derived by neutrophil degranulation during neutrophil-BBB interaction. The tetracycline group of antibiotics may suppress MMP production and neutrophil degranulation.


We hypothesize that migraine is a primary neuroinflammatory disorder. We will address this theory by measuring serum biomarkers in healthy controls and after one of three abortive therapy strategies for acute migraine attacks and inter-ictally. We intend to investigate known neuroinflammatory biomarkers with a focus on BBB breakdown during acute migraine attacks and assess marker responses to conventional treatment (triptans), novel MMP targeted therapy (doxycycline), or a combination of triptan and doxycycline. We will measure the effects of the interventions on neuroinflammatory markers for acute migraine attacks, clinical outcomes (headache relief and recurrence) for acute migraine attacks, inter-ictal neuroinflammatory load per serum biomarkers in migraineurs versus healthy controls, and neuroinflammatory markers correlation with headache duration and peak headache intensity during acute migraine attacks.


To our knowledge, this trial will be the first systematic study on the use of a MMP inhibitor in episodic migraine. Our pilot project data will supplement future projects investigating novel therapeutic strategies such as MMP inhibitors in both migraine acute treatment and prevention.

Trial Registration NCT01653522, registered 07/23/2012.


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