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

September 22, 2023 updated by: Shalini Suresh Shah, University of California, Irvine

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

17

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Irvine, California, United States, 92697
        • Gottschalk Medical Plaza
      • Orange, California, United States, 92868
        • UC Irvine Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

8 years to 17 years (Child)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: OnabotulinumtoxinA/Saline Placebo
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.
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 Names:
  • Botox
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.
Other: Saline Placebo/OnabotulinumtoxinA
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.
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 Names:
  • Botox
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Frequency of Migraines
Time Frame: Baseline (4 weeks) and 12 weeks post each, respective intervention
The frequency of migraines in days.
Baseline (4 weeks) and 12 weeks post each, respective intervention
Intensity of Migraines
Time Frame: Baseline (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.
Baseline (4 weeks) and 12 weeks post each, respective intervention
Migraine Duration, in Hours
Time Frame: Baseline (4 weeks) and 12 weeks post each, respective intervention
Duration of migraines in hours.
Baseline (4 weeks) and 12 weeks post each, respective intervention
Pediatric Migraine Disability Score (PedMIDAS)
Time Frame: 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).
Baseline (4 weeks) and 12 weeks post each, respective intervention

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Functionality Improvement
Time Frame: Baseline (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).
Baseline (4 weeks) and 12 weeks post each, respective intervention
Difficulty Sleeping
Time Frame: Baseline (4 weeks) and 12 weeks post each, respective intervention
Subject reported having difficulty sleeping
Baseline (4 weeks) and 12 weeks post each, respective intervention
Hospital Admissions
Time Frame: Baseline (4 weeks) and 12 weeks post each, respective intervention
Admission to hospital
Baseline (4 weeks) and 12 weeks post each, respective intervention
Emergency Department (ED) Visits
Time Frame: Baseline (4 weeks) and 12 weeks post each, respective intervention
Subject visited an Emergency Department
Baseline (4 weeks) and 12 weeks post each, respective intervention
Home School
Time Frame: Baseline (4 weeks) and 12 weeks post, respective intervention
Subject is home schooled full-time.
Baseline (4 weeks) and 12 weeks post, respective intervention
School Plan Enrollment
Time Frame: Baseline (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.
Baseline (4 weeks) and 12 weeks post each, respective intervention
Duration of Benefit
Time Frame: Baseline (4 weeks) and 12 weeks post each, respective intervention
The duration of benefit in weeks
Baseline (4 weeks) and 12 weeks post each, respective intervention
Concomitant Headache Medications
Time Frame: Baseline (4 weeks) and 12 weeks post each, respective intervention
Number of concomitant headache medications taken
Baseline (4 weeks) and 12 weeks post each, respective intervention

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Frequency of Migraines | Open-label Period
Time Frame: 24-48 weeks post-baseline 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
Intensity of Migraines | Open-Label Period
Time Frame: 24-48 weeks post-baseline 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
Pediatric Migraine Disability Score (PedMIDAS) | Open-Label Period
Time Frame: 24-48 weeks post-baseline 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
Duration of Migraine | Open-Label Period
Time Frame: 24-48 weeks post-baseline 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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, Irvine

Collaborators

American Society of Regional Anesthesia

Investigators

  • Principal Investigator: Shalini S Shah, MD, Assistant Clinical Professor

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2017

Primary Completion (Actual)

November 30, 2018

Study Completion (Actual)

April 20, 2020

Study Registration Dates

First Submitted

February 8, 2017

First Submitted That Met QC Criteria

February 13, 2017

First Posted (Actual)

February 16, 2017

Study Record Updates

Last Update Posted (Actual)

October 18, 2023

Last Update Submitted That Met QC Criteria

September 22, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20163108
  • UCIANES09 (Other Identifier: University of California, Irvine)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Migraine Disorders

Clinical Trials on OnabotulinumtoxinA

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in South Korea

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe