Childhood and Adolescent Migraine Prevention (CHAMP) study: a double-blinded, placebo-controlled, comparative effectiveness study of amitriptyline, topiramate, and placebo in the prevention of childhood and adolescent migraine

Abstract

Background: Migraine is one of the most common health problems for children and adolescents. If not successfully treated, it can impact patients and families with significant disability due to loss of school, work, and social function. When headaches become frequent, it is essential to try to prevent the headaches. For children and adolescents, this is guided by extrapolation from adult studies, a limited number of small studies in children and adolescents and practitioner preference. The aim of the Childhood and Adolescent Migraine Prevention (CHAMP) study is to determine the most effective preventive agent to use in children and adolescents.

Methods: CHAMP is a double-blinded, placebo-controlled, multicenter, comparative effectiveness study of amitriptyline and topiramate for the prevention of episodic and chronic migraine, designed to mirror real-world practice, sponsored by the US National Institute of Neurological Disorders and Stroke/National Institutes of Health (U01NS076788). The study will recruit 675 subjects between the ages of 8 and 17 years old, inclusive, who have migraine with or without aura or chronic migraine as defined by the International Classification of Headache Disorders, 2nd Edition, with at least 4 headaches in the 28 days prior to randomization. The subjects will be randomized in a 2:2:1 (amitriptyline: topiramate: placebo) ratio. Doses are weight based and will be slowly titrated over an 8-week period to a target dose of 1 mg/kg of amitriptyline and 2 mg/kg of topiramate. The primary outcome will be a 50% reduction in headache frequency between the 28-day baseline and the final 28 days of treatment (weeks 20-24).

Conclusions: The goal of the CHAMP study is to obtain level 1 evidence for the effectiveness of amitriptyline and topiramate in the prevention of migraine in children and adolescents. If this study proves to be positive, it will provide information to the practicing physician as how to best prevent migraine in children and adolescents and subsequently improve the disability and outcomes.

Trial registration: ClinicalTrials.gov NCT01581281.

Figure 1

Visit Sequence. Subjects are seen at 8 visits over the duration of the study with additional phone visits during the titration phase and after treatment phase for safety and tolerability assessment. Screening visit includes identification of subjects, validation of their inclusion and exclusion, baseline assessment, and study education. At Randomization visit, inclusion and exclusion is reassessed, safety and baseline assessment validated and calendar reviewed prior to randomization. Titration visits (in person and via phone discussion) will review tolerability of titration, allowing for adjustment as needed (Figure 2) and continued education. During Treatment/Maintenance phase subject will have safety evaluations (visit 5 and 8) and tolerability evaluated (visit 5, 6, 7 and 8) and continuing review of procedures with reinforcement of diary completion (visit 7) before final assessment (visit 8).Washout (phone 1) and final assessment (phone 2 – 28 days after completion of all medication) will assess overall response and tolerability.

Figure 2

Titration Plan. Subjects will start titration at randomization visit (visit 2, 0 weeks of medication). At 2 week intervals, subjects will be assessed for tolerability of medication treatment. At each of these nodal points, an assessment is made as to whether to continue increasing the titration, holding the current dose, returning to the previous dose (i.e, dose reduction). All choices are available at each nodal point. However, if 2 reduction are made, subjects will be terminated from the study and proceed to visit 8 assessment. If there is a dosage hold or reduction, subjects will be allowed to have an additional 2 weeks of titration in order to maximize dosing.