Effectiveness of Onabotulinumtoxin A (Botox) in Pediatric Patients Experiencing Migraines: A Study in the Pediatric Pain Population

Medical Literature approximates one in three children will experience chronic headaches in
their lifetime, which increases as children reach adolescence. Migraines make up nearly 60%
of all visits to a pediatric headache specialist. Studies have demonstrated the negative
impact of having childhood migraine on overall quality of life is similar to pediatric
cancer, heart disease and rheumatic disease. As the frequency of migraine attacks increase,
so does proportionally the child's disability in lost school time and family and social
interactions, all of which may lead in turn to economic disability. Studies estimate the
health care costs are 70% higher for a family with a migraine than a non-migraine affected
family, and direct medical costs for children with migraine are reported to be similar to
those for adults. A study published in JAMA 2003 found that health care costs, work-related
disability for parents and lost educational opportunity for the child leads to an annual
economic impact in the US of approximately $36 billion due to both direct medical costs and
lost productivity into adulthood.

Onaboutlinum (BOTOX) is currently FDA approved as a very successful treatment to prevent
migraines in adults, however not yet children. Current treatments for migraine in children
appear to be insufficient. No trials currently exist in literature prospectively studying
onabotulinumtoxinA for efficacy and/or safety for indication of pediatric migraine, although
significant contributions have been made by retrospective case series over the last 10 years.

This research will be the first investigator-initiated study to study BOTOX (R) in children
prospectively in a randomized controlled placebo, cross-over study. The overriding rationale
is to demonstrate efficacy, tolerability and safety of onabotulinumtoxinA for pediatric
migraine and thereby potentially hasten the lengthy process to evaluate BOTOX® for approval
in the pediatric population.

Inclusion Criteria:

- Children aged 8 - 17 years of age with a history of migraine meeting the criteria
established in ICHD-II (2004), Section 1. Patients will provide at least 28-day
baseline data in the form in the daily diary and must have at least 15 days of
reported headache during this period, with at least 4 distinct episodes lasting at
least 4 hours each.

Exclusion Criteria:

- Previous use of botulinum toxin of any serotype for any reason

- Pregnancy.

- Diagnosis of Myasthenia gravis, Eaton Lambert Syndrome, Amyotrophic Lateral Sclerosis

- Treatment of headache using acupuncture, transcutaneous electrical stimulation (TENS),
cranial traction, dental splints, or injection of anesthetics/steroids within 4 weeks
prior to the week of screening visit