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, multi-center, 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.

Cognitive Behavioral Therapy Plus Amitriptyline for Chronic Migraine in Children and Adolescents

“…Although amitriptyline is the most common preventative medication for headaches worldwide, 11 and is recommended by national practice parameters and open-label studies, 12,14 its effectiveness compared with placebo in youth remains unknown. 8,33,36 Using amitriptyline as a constant in this study allowed for a clear comparison of CBT with headache education.…”

Treatment Adherence in Child and Adolescent Chronic Migraine Patients

“…Thus, future studies evaluating adherence to pediatric migraine treatment should include objective measures of adherence. For example, electronic medication monitoring devices or collecting serum levels of active medications 32 could be used to more directly assess medication adherence. The current study attempted to utilize pill counts; however, pill counts were started late in the trial and were largely unsuccessful due to the majority of patients not returning any of their blister packs.…”

The optimal management of headaches in children and adolescents

“…Although its efficacy in pediatrics has not been evaluated in randomized controlled trials, it continues to be one of the most widely used agents. It is often titrated slowly over a period of 8-12 weeks, increasing by 0.25 mg/kg/day every 2 weeks [Hershey et al 2000[Hershey et al , 2013. The side effects of amitriptyline include dry mouth, dry eyes, lightheadedness, dizziness, constipation, increased appetite, somnolence, and may unmask a prolonged QT most often at doses of greater than 1 mg/kg.…”