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

NCT03055767 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 20163108UCIANES09
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 2

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.

Conditions

Migraine Disorders; Headache, Migraine; Pediatrics

Outcome Measures

Primary Outcomes (4)

• Frequency of Migraines

  The frequency of migraines in days.

  Baseline (4 weeks) and 12 weeks post each, respective intervention

• 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

• Migraine Duration, in Hours

  Duration of migraines in hours.

  Baseline (4 weeks) and 12 weeks post each, respective intervention

• 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 Outcomes (8)

• Functionality Improvement

  Baseline (4 weeks) and 12 weeks post each, respective intervention

• Difficulty Sleeping

  Baseline (4 weeks) and 12 weeks post each, respective intervention

• Hospital Admissions

  Baseline (4 weeks) and 12 weeks post each, respective intervention

• Emergency Department (ED) Visits

  Baseline (4 weeks) and 12 weeks post each, respective intervention

• Home School

  Baseline (4 weeks) and 12 weeks post, respective intervention

Other Outcomes (4)

• Frequency of Migraines | Open-label Period

  24-48 weeks post-baseline period

• Intensity of Migraines | Open-Label Period

  24-48 weeks post-baseline period

• Pediatric Migraine Disability Score (PedMIDAS) | Open-Label Period

  24-48 weeks post-baseline period

Study Arms (2)

OnabotulinumtoxinA/Saline Placebo

OTHER

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; Other: Placebo (Saline)

Saline Placebo/OnabotulinumtoxinA

OTHER

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; Other: Placebo (Saline)

Interventions

OnabotulinumtoxinA DRUG

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.

Also known as: Botox

OnabotulinumtoxinA/Saline Placebo; Saline Placebo/OnabotulinumtoxinA

Placebo (Saline) OTHER

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 Placebo; Saline Placebo/OnabotulinumtoxinA

Eligibility Criteria

• Age: 8 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, Irvine: lead
• American Society of Regional Anesthesia: collaborator

Study Sites (2)

Gottschalk Medical Plaza

Irvine, California, 92697, United States

Location

UC Irvine Medical Center

Orange, California, 92868, United States

Location

Related Publications (14)

• 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.

  PMID: 21883197 BACKGROUND

• 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.

  PMID: 20487038 BACKGROUND

• 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.

  PMID: 20933173 BACKGROUND

• 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.

  PMID: 23303551 BACKGROUND

• 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.

  PMID: 26521123 BACKGROUND

• 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.

  PMID: 19835236 BACKGROUND

• 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.

  PMID: 7596620 BACKGROUND

• 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.

  PMID: 23594025 BACKGROUND

• 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.

  PMID: 22288433 BACKGROUND

• 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.

  PMID: 22274570 BACKGROUND

• 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.

  PMID: 24760491 BACKGROUND

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

  PMID: 25772998 BACKGROUND

• 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.

  PMID: 26695061 BACKGROUND

• Shah S, Calderon MD, Crain N, Pham J, Rinehart J. Effectiveness of onabotulinumtoxinA (BOTOX) in pediatric patients experiencing migraines: a randomized, double-blinded, placebo-controlled crossover study in the pediatric pain population. Reg Anesth Pain Med. 2021 Jan;46(1):41-48. doi: 10.1136/rapm-2020-101605. Epub 2020 Oct 26.

  PMID: 33106278 DERIVED

MeSH Terms

Conditions

Migraine Disorders

Interventions

Botulinum Toxins, Type A; Sodium Chloride

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

A lack of diversity in subject demographics and age. Didn't control for patients seeking alternative therapies during the study period, nor attempt to control concomitant medications. Patients with comorbidities can have an impact on the treatment effect. PedMIDAS may not account for seasonal changes or patients with modified school schedules. Continuation of baseline therapy is a confounding variable. Pain diary records required follow-up. Data collection relied in part on subject recall.

Results Point of Contact

• Title: Shalini Shah, MD
• Organization: University of California, Irvine | Dept. of Anesthesiology & Perioperative Care

ssshah1@hs.uci.edu

(949) 824-7246

Study Officials

• Shalini S Shah, MD

  Assistant Clinical Professor

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice Chair, Pain Management

Study Record Dates

• First Submitted: February 8, 2017
• First Posted: February 16, 2017
• Study Start: March 1, 2017
• Primary Completion: November 30, 2018
• Study Completion: April 20, 2020
• Last Updated: October 18, 2023
• Results First Posted: October 18, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)