Cabergoline for migraine prevention (PROTECT): Protocol for a randomized, placebo-controlled, double-blind trial

Cabergoline, a dopamine receptor agonist, has shown beneficial effects as a preventive treatment for migraine, with no serious adverse events reported. This study aims to evaluate whether cabergoline is superior to placebo in reducing monthly migraine days (MMD), while assessing safety and tolerability. In a randomized, parallel-group, placebo-controlled, double-blind superiority phase II trial, 150 adults with 4–14 MMD will be included. Participants are randomized (1:1:1) to cabergoline 0.5 mg, cabergoline 1.0 mg or placebo once weekly as add-on treatment for 12 weeks. In a 12-week open-label extension, all participants, including those initially assigned to placebo, will be re-randomized (1:1) to cabergoline 0.5 mg or 1.0 mg once weekly to assess sustained effects and safety. The primary outcome is change in MMD from baseline to the final four weeks of the double-blind phase. Key secondary outcomes include ≥50% responder rate, change in the number of moderate-to-severe headache days, acute medication use and patient-reported outcomes (PGIC, HIT-6, MIDAS, WPAI). Exploratory analyses include biomarkers, pharmacogenetics and cost-effectiveness. Analyses will follow the intention-to-treat principle.