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

Migraine Disorders Clinical Trial

Official title:

Effectiveness of Onabotulinumtoxin A (Botox) in Pediatric Patients Experiencing Migraines: A Randomized Double Blinded Placebo Cross-over Study in the Pediatric Pain Population

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03055767
• Other study ID #: 20163108
• Secondary ID: UCIANES09
• Status: Completed
• Phase: Phase 2
• Start date: March 1, 2017
• Est. completion date: April 20, 2020

Study information

• Verified date: September 2023
• Source: University of California, Irvine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: April 20, 2020
• Est. primary completion date: November 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Headache
• Headache, Migraine
• Migraine Disorders
• Pediatrics

Intervention

Drug:
• OnabotulinumtoxinA
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.

Other:
• Placebo (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.

Locations

Country	Name	City	State
United States	Gottschalk Medical Plaza	Irvine	California
United States	UC Irvine Medical Center	Orange	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, Irvine	American Society of Regional Anesthesia

Country where clinical trial is conducted

United States, 

References & Publications (13)

Ahmed K, Oas KH, Mack KJ, Garza I. Experience with botulinum toxin type A in medically intractable pediatric chronic daily headache. Pediatr Neurol. 2010 Nov;43(5):316-9. doi: 10.1016/j.pediatrneurol.2010.06.001. — View Citation

Aurora SK, Winner P, Freeman MC, Spierings EL, Heiring JO, DeGryse RE, VanDenburgh AM, Nolan ME, Turkel CC. OnabotulinumtoxinA for treatment of chronic migraine: pooled analyses of the 56-week PREEMPT clinical program. Headache. 2011 Oct;51(9):1358-73. doi: 10.1111/j.1526-4610.2011.01990.x. Epub 2011 Aug 29. — View Citation

Bonfert M, Straube A, Schroeder AS, Reilich P, Ebinger F, Heinen F. Primary headache in children and adolescents: update on pharmacotherapy of migraine and tension-type headache. Neuropediatrics. 2013 Feb;44(1):3-19. doi: 10.1055/s-0032-1330856. Epub 2013 Jan 9. — View Citation

Brodsky JR, Cusick BA, Zhou G. Evaluation and management of vestibular migraine in children: Experience from a pediatric vestibular clinic. Eur J Paediatr Neurol. 2016 Jan;20(1):85-92. doi: 10.1016/j.ejpn.2015.09.011. Epub 2015 Oct 22. — View Citation

Chan VW, McCabe EJ, MacGregor DL. Botox treatment for migraine and chronic daily headache in adolescents. J Neurosci Nurs. 2009 Oct;41(5):235-43. doi: 10.1097/jnn.0b013e3181aaa98f. — View Citation

Dodick DW, Turkel CC, DeGryse RE, Aurora SK, Silberstein SD, Lipton RB, Diener HC, Brin MF; PREEMPT Chronic Migraine Study Group. OnabotulinumtoxinA for treatment of chronic migraine: pooled results from the double-blind, randomized, placebo-controlled phases of the PREEMPT clinical program. Headache. 2010 Jun;50(6):921-36. doi: 10.1111/j.1526-4610.2010.01678.x. Epub 2010 May 7. — View Citation

Hermann C, Kim M, Blanchard EB. Behavioral and prophylactic pharmacological intervention studies of pediatric migraine: an exploratory meta-analysis. Pain. 1995 Mar;60(3):239-55. doi: 10.1016/0304-3959(94)00210-6. — View Citation

Hershey AD, Powers SW, Coffey CS, Eklund DD, Chamberlin LA, Korbee LL; CHAMP Study Group. 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. Headache. 2013 May;53(5):799-816. doi: 10.1111/head.12105. Epub 2013 Apr 17. — View Citation

Jacobs H, Gladstein J. Pediatric headache: a clinical review. Headache. 2012 Feb;52(2):333-9. doi: 10.1111/j.1526-4610.2011.02086.x. Epub 2012 Jan 30. Erratum In: Headache. 2012 Mar;52(3):527. Dosage error in article text. — View Citation

Kabbouche M, O'Brien H, Hershey AD. OnabotulinumtoxinA in pediatric chronic daily headache. Curr Neurol Neurosci Rep. 2012 Apr;12(2):114-7. doi: 10.1007/s11910-012-0251-1. — View Citation

Kacperski J, Hershey AD. Preventive drugs in childhood and adolescent migraine. Curr Pain Headache Rep. 2014 Jun;18(6):422. doi: 10.1007/s11916-014-0422-7. — View Citation

Tajti J, Szok D, Csati A, Vecsei L. Prophylactic Drug Treatment of Migraine in Children and Adolescents: An Update. Curr Pain Headache Rep. 2016 Jan;20(1):1. doi: 10.1007/s11916-015-0536-6. — View Citation

Yonker M, Mangum T. Migraine management in children. Curr Neurol Neurosci Rep. 2015 May;15(5):20. doi: 10.1007/s11910-015-0540-6. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Frequency of Migraines | Open-label Period	The frequency of migraines during the open-label period (2 additional rounds of onabotulinumtoxinA) as compared to the cross-over period.	24-48 weeks post-baseline period
Other	Intensity of Migraines | Open-Label Period	Intensity of migraines during the the open-label period (2 additional rounds of onabotulinumtoxinA) as compared to the cross-over period.; Intensity based on 0-10 Pain Numeric Rating Score (NRS). The higher the score, the more intense the pain.	24-48 weeks post-baseline period
Other	Pediatric Migraine Disability Score (PedMIDAS) | Open-Label Period	The PedMIDAS the open-label period (2 additional rounds of onabotulinumtoxinA) as compared to the cross-over period.; 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).	24-48 weeks post-baseline period
Other	Duration of Migraine | Open-Label Period	Duration of migraine in hours during the open-label period (2 additional rounds of onabotulinumtoxinA) as compared to the cross-over period.	24-48 weeks post-baseline period
Primary	Frequency of Migraines	The frequency of migraines in days.	Baseline (4 weeks) and 12 weeks post each, respective intervention
Primary	Intensity of Migraines	Median intensity of migraines based on 0-10 Pain Numeric Rating Score (NRS). The higher the score, the more intense the pain.	Baseline (4 weeks) and 12 weeks post each, respective intervention
Primary	Migraine Duration, in Hours	Duration of migraines in hours.	Baseline (4 weeks) and 12 weeks post each, respective intervention
Primary	Pediatric Migraine Disability Score (PedMIDAS)	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).	Baseline (4 weeks) and 12 weeks post each, respective intervention
Secondary	Functionality Improvement	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).	Baseline (4 weeks) and 12 weeks post each, respective intervention
Secondary	Difficulty Sleeping	Subject reported having difficulty sleeping	Baseline (4 weeks) and 12 weeks post each, respective intervention
Secondary	Hospital Admissions	Admission to hospital	Baseline (4 weeks) and 12 weeks post each, respective intervention
Secondary	Emergency Department (ED) Visits	Subject visited an Emergency Department	Baseline (4 weeks) and 12 weeks post each, respective intervention
Secondary	Home School	Subject is home schooled full-time.	Baseline (4 weeks) and 12 weeks post, respective intervention
Secondary	School Plan Enrollment	Subject is enrolled in a school plan such as IEP, 504 plan, or similar modified school schedule.	Baseline (4 weeks) and 12 weeks post each, respective intervention
Secondary	Duration of Benefit	The duration of benefit in weeks	Baseline (4 weeks) and 12 weeks post each, respective intervention
Secondary	Concomitant Headache Medications	Number of concomitant headache medications taken	Baseline (4 weeks) and 12 weeks post each, respective intervention