NCT01581281

Brief Summary

The purpose of this research study is to test two medicines for migraine prevention in children and adolescents.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
488

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Jun 2012

Typical duration for phase_3

Geographic Reach
1 country

35 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 16, 2011

Completed
4 months until next milestone

First Posted

Study publicly available on registry

April 20, 2012

Completed
1 month until next milestone

Study Start

First participant enrolled

June 1, 2012

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2015

Completed
9 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2016

Completed
1.6 years until next milestone

Results Posted

Study results publicly available

August 10, 2017

Completed
Last Updated

August 10, 2017

Status Verified

July 1, 2017

Enrollment Period

2.8 years

First QC Date

December 16, 2011

Results QC Date

November 16, 2016

Last Update Submit

July 11, 2017

Conditions

Keywords

PediatricChildrenAdolescentHeadacheMigraine

Outcome Measures

Primary Outcomes (1)

  • Number (Percentage) of Participants Reporting a ≥ 50% Reduction in Headache Days

    The primary endpoint was a ≥ 50% reduction in headache frequency from the 28 days (4 weeks) baseline period prior to randomization to the last 28 days (4 weeks) of the trial. Headache frequency was defined as the number of days with headache for a given four week 28 day (4 week) period. A headache day was defined as any day during which any headache occurs within a 24 hour period, starting and ending at midnight. For each participant, the primary endpoint involved a determination of whether a 50% or greater reduction in headache frequency was observed during the last 4 weeks of active treatment as compared with the headache frequency during the 4-week baseline period. Results were compared across the three treatment groups.

    4 week baseline period and last 4 weeks of the 24-week trial

Secondary Outcomes (4)

  • Change in Absolute Headache Disability Score on PedMIDAS

    baseline and 24 week endpoint

  • Change in Number of Headache Days

    4 week baseline period and last 4 weeks of the 24-week trial

  • Tolerability, as Indicated by the Number (Percentage) of Participants That Completed the 24-week Treatment Phase

    24 weeks

  • Occurrence of Treatment Emergent Serious Adverse Events

    24 weeks of the trial

Study Arms (3)

Amitriptyline

ACTIVE COMPARATOR

Drug to be administered twice daily.

Drug: Amitriptyline

Topiramate

ACTIVE COMPARATOR

Drug to be administered twice daily.

Drug: Topiramate

Placebo

PLACEBO COMPARATOR

To be administered twice daily.

Drug: Placebo

Interventions

Amitriptyline will be administered twice daily at home during the 8-week titration period followed by a 16 week maintenance phase of the highest tolerated dose. The morning dose is a placebo pill. Dosing of amitriptyline will be weight-based.

Amitriptyline

Topiramate will be administered twice daily at home during the 8-week titration period followed by a 16 week maintenance phase of the highest tolerated dose. Dosing of topiramate will be weight-based.

Topiramate

Placebo will be administered twice daily at home during the 8-week titration period followed by a 16 week maintenance period.

Placebo

Eligibility Criteria

Age8 Years - 17 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • Migraine with or without aura (International Classification of Headache Disorders, 2nd Edition (ICHD-II) or chronic migraine (ICHD-II revised)
  • Migraine frequency based upon prospective headache diary of 28 days must be ≥ 4. Migraine frequency defined as any migraine during one day in the 28 day baseline period (1)
  • PedMIDAS Disability Score \> 10, indicating at least mild disruption in daily activities and \< 140, indicating extreme disability that may require more comprehensive, multi-component therapy
  • Females or males 8-17 years, inclusive
  • Migraine frequency is defined as the period from the onset to the stop time of painful migraine symptoms not to exceed 24 hours with the clock starting at midnight. If painful symptoms last longer than 24 hours, this is considered a new and distinct migraine headache. If painful symptoms recur within 24 hours of initial onset, this is considered part of the initial migraine episode and would be counted as one migraine.

You may not qualify if:

  • Continuous migraine defined as an unrelenting headache for a 28 day period
  • Weight less than 30 kg or greater than 120 kg
  • Unwilling to avoid taking non-specific acute medication such as NSAIDS (e.g., ibuprofen), more than 3 times per week, or migraine specific acute medications such as triptans more than 6 times per month
  • Currently taking other prophylactic anti-migraine medication within a period equivalent to 2 weeks of that medication before entering the screening phase, or the use of Botulinum toxin (Botox®) within 3 months of entering the screening phase
  • Subjects who have previously failed an adequate trial of AMI or TPM for prophylaxis of at least 3 months duration at doses recommended for migraine relief because of lack of efficacy or adverse events(2)
  • Current use of disallowed medications/products: opioids, antipsychotics, antimanics, barbiturates, benzodiazepines, muscle relaxants, sedatives, tramadol, nutraceuticals, SSRIs, or SSNRIs
  • Known history of allergic reaction or anaphylaxis to AMI or TPM
  • Abnormal findings on ECG at baseline, particularly lengthening of the QT interval greater than or equal to 450 msec
  • Subject is pregnant or has a positive pregnancy test
  • Subject is sexually active and not using a medically acceptable form of contraception
  • Diagnosis of epilepsy or other neurological diseases
  • History of kidney stones
  • Inability to swallow pills after using behavioral techniques if indicated between screening visit and baseline visit (3)
  • Present psychiatric disease as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM IV) (e.g. psychosis, bipolar disorder, major depression, generalized anxiety disorder), alcohol or drug dependence, or documented developmental delays or impairments (e.g., autism, cerebral palsy, or mental retardation) that, in the opinion of the site investigator, would interfere with adherence to study requirements or safe participation in the trial
  • Any and all other diagnoses or conditions which in the opinion of the site investigator, that would prevent the patient from being a suitable candidate for the study or interfere with the medical care needs of the study subject
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (35)

Phoenix Children's Medical Group

Phoenix, Arizona, 85016, United States

Location

University of California-San Francisco Headache Center

San Francisco, California, 94115, United States

Location

Stanford Hospital and Clinics

Stanford, California, 94305, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Colorado Springs Neurological Associates

Colorado Springs, Colorado, 80907, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Premiere Research Institute

West Palm Beach, Florida, 33407, United States

Location

Atlanta Headache Specialists

Atlanta, Georgia, 30342, United States

Location

Josephson Wallack Munshower Neurology Research

Indianapolis, Indiana, 46237, United States

Location

Children's Mercy Hospital

Kansas City, Kansas, 66160, United States

Location

University of Louisville Health Sciences Center

Louisville, Kentucky, 40292, United States

Location

University of Maryland School of Medicine

Baltimore, Maryland, 21201, United States

Location

Children's Hospital of Boston

Waltham, Massachusetts, 02453, United States

Location

New England Regional Headache Center

Worcester, Massachusetts, 01605, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Saint Louis University

St Louis, Missouri, 63104, United States

Location

University of Nevada

Reno, Nevada, 89502, United States

Location

Dent Neurological Institute

Amherst, New York, 14226, United States

Location

Winthrop University Hospital

Mineola, New York, 11501, United States

Location

The Headache Institute at Roosevelt Hospital

New York, New York, 10019, United States

Location

Schenectady Neurological Constultants, PC

Schenectady, New York, 12308, United States

Location

Akron Children's Hospital

Akron, Ohio, 44308, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

The Children's Hospital, Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Oklahoma Health Sciences

Oklahoma City, Oklahoma, 73104, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Preferred Clinical Research

Pittsburgh, Pennsylvania, 15236, United States

Location

LeBonheur Children's Hospital

Memphis, Tennessee, 38105, United States

Location

Dallas Pediatric Neurology Associates

Dallas, Texas, 75230, United States

Location

Scott and White Healthcare

Temple, Texas, 76508, United States

Location

Primary Children's Medical Center

Salt Lake City, Utah, 84108, United States

Location

Eastern Virginia Medical School

Norfolk, Virginia, 23510, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Marshfield Clinic

Marshfield, Wisconsin, 54449, United States

Location

Related Publications (4)

  • Reidy BL, Powers SW, Coffey CS, Chamberlin LA, Ecklund DJ, Klingner EA, Yankey JW, Korbee LL, Porter LL, Peugh J, Kabbouche MA, Kacperski J, Hershey AD; CHAMP Investigators. Multimodal Assessment of Medication Adherence Among Youth With Migraine: An Ancillary Study of the CHAMP Trial. J Pediatr Psychol. 2022 Apr 8;47(4):376-387. doi: 10.1093/jpepsy/jsab123.

  • Reidy BL, Peugh J, Hershey AD, Coffey CS, Chamberlin LA, Ecklund DJ, Klingner EA, Yankey JW, Korbee LL, Porter LL, Kabbouche MA, Kacperski J, Powers SW. Trajectory of treatment response in the child and adolescent migraine prevention (CHAMP) study: A randomized clinical trial. Cephalalgia. 2022 Jan;42(1):44-52. doi: 10.1177/03331024211033551. Epub 2021 Aug 17.

  • Powers SW, Coffey CS, Chamberlin LA, Ecklund DJ, Klingner EA, Yankey JW, Korbee LL, Porter LL, Hershey AD; CHAMP Investigators. Trial of Amitriptyline, Topiramate, and Placebo for Pediatric Migraine. N Engl J Med. 2017 Jan 12;376(2):115-124. doi: 10.1056/NEJMoa1610384. Epub 2016 Oct 27.

  • 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.

MeSH Terms

Conditions

Migraine DisordersHeadache

Interventions

AmitriptylineTopiramate

Condition Hierarchy (Ancestors)

Headache Disorders, PrimaryHeadache DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesPainNeurologic ManifestationsSigns and SymptomsPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

DibenzocycloheptenesBenzocycloheptenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic CompoundsFructoseHexosesMonosaccharidesSugarsCarbohydratesKetoses

Results Point of Contact

Title
Scott Powers, PhD
Organization
Cincinnati Children's Hospital Medical Center

Study Officials

  • Scott W. Powers, PhD

    Children's Hospital Medical Center, Cincinnati

    PRINCIPAL INVESTIGATOR
  • Andrew D. Hershey, MD, PhD

    Children's Hospital Medical Center, Cincinnati

    PRINCIPAL INVESTIGATOR
  • Christopher S. Coffey, PhD

    University of Iowa

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 16, 2011

First Posted

April 20, 2012

Study Start

June 1, 2012

Primary Completion

April 1, 2015

Study Completion

January 1, 2016

Last Updated

August 10, 2017

Results First Posted

August 10, 2017

Record last verified: 2017-07

Data Sharing

IPD Sharing
Will share

De-identified datasets and associated documentation will be submitted to NINDS for archiving and public access, consistent with current NINDS data sharing policy.

Locations