To demonstrate that calcitonin gene-related peptide (CGRP) induces headache exacerbation with migraine-like features in patients with persistent post-traumatic headache (PTH) attributed to mild traumatic brain injury (TBI).
A randomized, double-blind, placebo-controlled, 2-way crossover study. Analyses were intention-to-treat. Eligible patients were aged 18 to 65 years and had a history of persistent PTH after mild TBI for at least 12 months. Patients were randomized to receive intravenous infusion 1.5 μg/min of CGRP or placebo (isotonic saline) over 20 minutes on two separate experimental days. A 12-hour observational period was used to evaluate the following outcomes: 1) difference in incidence of headache exacerbation with migraine-like features, 2) difference in area under the curve for headache intensity scores.
Thirty patients (mean age, 37 years; 25 women [83%]) were randomized and completed the study. During the 12-hour observational period, 21 of 30 patients (70%) developed headache exacerbation with migraine-like features after CGRP, compared with six patients (20%) after placebo (P < 0.001). The baseline-corrected area under the curve for headache intensity scores was significantly larger after CGRP, compared with placebo (P < 0.001).
Patients with persistent PTH are hypersensitive to CGRP, which underscores its pathophysiological importance. Furthermore, CGRP-targeted therapies might provide a novel mechanism-based treatment option for patients with persistent PTH.
Clinical.Trials.gov (NCT03791515). This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.