Rationale and design for a randomized, single-center, double-blind, sham-controlled study of non-invasive vagus nerve stimulation for treatment of post-traumatic headache

Abstract

ObjectiveEvaluate the efficacy and safety of non-invasive vagus nerve stimulation (nVNS) for the treatment of post-traumatic headache (PTH).BackgroundWorldwide, ∼69 million people per year sustain a traumatic brain injury (TBI), many of whom develop PTH. Clinicians often treat PTH with drugs approved for primary headache disorders, and many patients self-treat with over-the-counter agents but have inadequate pain relief. There has been little study of therapies for PTH, and safe, effective treatments are needed.Design/MethodsThis randomized, double-blind, sham-controlled, parallel-group pilot study is enrolling adults who present 1–4 weeks after a head injury, meet International Classification of Headache Disorders 3rd edition (ICHD-3) criteria for acute headache attributed to mild TBI, and have ≥2 headaches/week with a migraine or probable migraine phenotype. After a 2-week run-in period, subjects are randomly assigned (1:1 allocation) to receive daily preventive therapy and as-needed acute treatment with nVNS or a sham device. Preventive therapy consists of two 120-second stimulations 3 times daily. Acute treatment comprises 2 stimulations at headache onset and 2 stimulations 20 minutes after the start of initial treatment. Subjects are not to use acute rescue medication for 120 minutes post-treatment. One North American site will enroll ≤80 subjects. The expected duration is 12 months (enrollment, 9 months; participation, 14 weeks).ResultsThe primary effectiveness end point is decrease in pain (on a 7-point scale) 60 minutes post-treatment for all treated headache attacks. Secondary end points include decrease in the frequency of headache days between the run-in period and the last 2 weeks of the double-blind period and responder rates (ie, percentages of subjects with ≥50% decrease in attack frequency). The primary safety end point is the incidence of treatment-related serious adverse events.ConclusionsThis study will assess the efficacy and safety of nVNS as a novel therapy for PTH.