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

Phase 2
Completed
Conditions
Migraine Disorders
Headache, Migraine
Pediatrics
Interventions
Other: Placebo (Saline)
Registration Number
NCT03055767
Lead Sponsor
University of California, Irvine
Brief Summary

The purpose of the research is to examine the outcomes of pediatric patients receiving Botulinum toxin type A (Botox ®) for the treatment of migraine. There is limited literature on the effectiveness of Botox ® in the treatment of chronic neurological pain in pediatric patients, specifically in the treatment of migraines.

Detailed Description

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
17
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
OnabotulinumtoxinA/Saline PlaceboPlacebo (Saline)The AB subject group will receive OnabotulinumtoxinA in the first treatment and saline placebo in the second.Both groups will then receive OnabotulinumtoxinA in the last two treatments. There will be one treatment at the beginning of each 12 week block, meaning 4 treatments over the 48 week study period total. Progress check-ups will occur every 6 weeks during the study. Randomization will be via selection of sealed envelope.
Saline Placebo/OnabotulinumtoxinAPlacebo (Saline)The BA subject group will receive saline and then Onabotulinumtoxin. A.Both groups will then receive OnabotulinumtoxinA in the last two treatments. There will be one treatment at the beginning of each 12 week block, meaning 4 treatments over the 48 week study period total. Progress check-ups will occur every 6 weeks during the study. Randomization will be via selection of sealed envelope.
OnabotulinumtoxinA/Saline PlaceboOnabotulinumtoxinAThe AB subject group will receive OnabotulinumtoxinA in the first treatment and saline placebo in the second.Both groups will then receive OnabotulinumtoxinA in the last two treatments. There will be one treatment at the beginning of each 12 week block, meaning 4 treatments over the 48 week study period total. Progress check-ups will occur every 6 weeks during the study. Randomization will be via selection of sealed envelope.
Saline Placebo/OnabotulinumtoxinAOnabotulinumtoxinAThe BA subject group will receive saline and then Onabotulinumtoxin. A.Both groups will then receive OnabotulinumtoxinA in the last two treatments. There will be one treatment at the beginning of each 12 week block, meaning 4 treatments over the 48 week study period total. Progress check-ups will occur every 6 weeks during the study. Randomization will be via selection of sealed envelope.
Primary Outcome Measures
NameTimeMethod
Migraine Duration, in HoursBaseline (4 weeks) and 12 weeks post each, respective intervention

Duration of migraines in hours.

Pediatric Migraine Disability Score (PedMIDAS)Baseline (4 weeks) and 12 weeks post each, respective intervention

Pediatric Migraine Disability Score consists of 6 questions: 3 addressing school attendance and functioning, and 3 evaluating participation in events outside of school. The questionnaire is based on the patient's recall of the previous 3 months.

The questionnaire produces a raw score (0-10, 11-30, 31-50, \>50) corresponding to a disability grade with increasing severity (little to non, mild, moderate, and severe) which was coded (1, 2, 3, and 4).

Frequency of MigrainesBaseline (4 weeks) and 12 weeks post each, respective intervention

The frequency of migraines in days.

Intensity of MigrainesBaseline (4 weeks) and 12 weeks post each, respective intervention

Median intensity of migraines based on 0-10 Pain Numeric Rating Score (NRS). The higher the score, the more intense the pain.

Secondary Outcome Measures
NameTimeMethod
Hospital AdmissionsBaseline (4 weeks) and 12 weeks post each, respective intervention

Admission to hospital

Duration of BenefitBaseline (4 weeks) and 12 weeks post each, respective intervention

The duration of benefit in weeks

Concomitant Headache MedicationsBaseline (4 weeks) and 12 weeks post each, respective intervention

Number of concomitant headache medications taken

Difficulty SleepingBaseline (4 weeks) and 12 weeks post each, respective intervention

Subject reported having difficulty sleeping

School Plan EnrollmentBaseline (4 weeks) and 12 weeks post each, respective intervention

Subject is enrolled in a school plan such as IEP, 504 plan, or similar modified school schedule.

Functionality ImprovementBaseline (4 weeks) and 12 weeks post each, respective intervention

Improvement of functionality as determined by their Pediatric Migraine Disability Score (PedMIDAS). The PedMIDAS consists of 6 questions: 3 addressing school attendance and functioning, and 3 evaluating participation in events outside of school. The questionnaire is based on the patient's recall of the previous 3 months.

The questionnaire produces a raw score (0-10, 11-30, 31-50, \>50) corresponding to a disability grade with increasing severity (little to non, mild, moderate, and severe) which was coded (1, 2, 3, and 4).

Emergency Department (ED) VisitsBaseline (4 weeks) and 12 weeks post each, respective intervention

Subject visited an Emergency Department

Home SchoolBaseline (4 weeks) and 12 weeks post, respective intervention

Subject is home schooled full-time.

Trial Locations

Locations (2)

UC Irvine Medical Center

🇺🇸

Orange, California, United States

Gottschalk Medical Plaza

🇺🇸

Irvine, California, United States

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