The Childhood and Adolescent Migraine Prevention Study (CHAMP)

July 11, 2017 updated by: Children's Hospital Medical Center, Cincinnati

Amitriptyline and Topiramate in the Prevention of Childhood Migraine

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

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

The purpose of this research study is to test two medicines for migraine prevention in children and adolescents. The investigators want to see if amitriptyline and/or topiramate are better than placebo (sugar pill) in reducing headache frequency in children and adolescents ages 8 to 17 with migraines. At this time, there are no FDA approved medicines approved in the US for the prevention treatment of migraine headaches in children and adolescents.

Study Type

Interventional

Enrollment (Actual)

488

Phase

  • Phase 3

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
    • Arizona
      • Phoenix, Arizona, United States, 85016
        • Phoenix Children's Medical Group
    • California
      • San Francisco, California, United States, 94115
        • University of California-San Francisco Headache Center
      • Stanford, California, United States, 94305
        • Stanford Hospital and Clinics
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Children's Hospital Colorado
      • Colorado Springs, Colorado, United States, 80907
        • Colorado Springs Neurological Associates
    • District of Columbia
      • Washington, D.C., District of Columbia, United States, 20010
        • Children's National Medical Center
    • Florida
      • West Palm Beach, Florida, United States, 33407
        • Premiere Research Institute
    • Georgia
      • Atlanta, Georgia, United States, 30342
        • Atlanta Headache Specialists
    • Indiana
      • Indianapolis, Indiana, United States, 46237
        • Josephson Wallack Munshower Neurology Research
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • Children's Mercy Hospital
    • Kentucky
      • Louisville, Kentucky, United States, 40292
        • University of Louisville Health Sciences Center
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland School of Medicine
    • Massachusetts
      • Waltham, Massachusetts, United States, 02453
        • Children's Hospital of Boston
      • Worcester, Massachusetts, United States, 01605
        • New England Regional Headache Center
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • Missouri
      • Saint Louis, Missouri, United States, 63104
        • Saint Louis University
    • Nevada
      • Reno, Nevada, United States, 89502
        • University of Nevada
    • New York
      • Amherst, New York, United States, 14226
        • Dent Neurological Institute
      • Mineola, New York, United States, 11501
        • Winthrop University Hospital
      • New York, New York, United States, 10019
        • The Headache Institute at Roosevelt Hospital
      • Schenectady, New York, United States, 12308
        • Schenectady Neurological Constultants, PC
    • Ohio
      • Akron, Ohio, United States, 44308
        • Akron Children's Hospital
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center
      • Cleveland, Ohio, United States, 44195
        • The Children's Hospital, Cleveland Clinic
      • Columbus, Ohio, United States, 43205
        • Nationwide Children's Hospital
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Oklahoma Health Sciences
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia
      • Pittsburgh, Pennsylvania, United States, 15236
        • Preferred Clinical Research
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • LeBonheur Children's Hospital
    • Texas
      • Dallas, Texas, United States, 75230
        • Dallas Pediatric Neurology Associates
      • Temple, Texas, United States, 76508
        • Scott and White Healthcare
    • Utah
      • Salt Lake City, Utah, United States, 84108
        • Primary Children's Medical Center
    • Virginia
      • Norfolk, Virginia, United States, 23510
        • Eastern Virginia Medical School
    • Washington
      • Seattle, Washington, United States, 98105
        • Seattle Children's Hospital
    • Wisconsin
      • Marshfield, Wisconsin, United States, 54449
        • Marshfield Clinic

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

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

    1. 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.

Exclusion Criteria:

  • 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)"Previously failed an adequate trial of AMI or TPM" is defined as: dosage of 1mg/kg/day of AMI or 2 mg/kg/day of TPM; trial of at least 3 months duration; efficacy of having at least a 50% decrease in migraine frequency in response to drug therapy; or unable to tolerate taking the medication due to treatment-related side effects.

    (3)Subjects who cannot swallow pills at the time of the screening visit will be given a training session using behavioral techniques. Upon return for baseline visit, if the subject continues to be unable to swallow pills, the subject will be excluded from the study.

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: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Amitriptyline
Drug to be administered twice daily.
Drug: Amitriptyline
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.
ACTIVE_COMPARATOR: Topiramate
Drug to be administered twice daily.
Drug: Topiramate
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.
PLACEBO_COMPARATOR: Placebo
To be administered twice daily.
Drug: Placebo
Placebo will be administered twice daily at home during the 8-week titration period followed by a 16 week maintenance period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number (Percentage) of Participants Reporting a ≥ 50% Reduction in Headache Days
Time Frame: 4 week baseline period and last 4 weeks of the 24-week trial

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Absolute Headache Disability Score on PedMIDAS
Time Frame: baseline and 24 week endpoint

The PedMIDAS scale which evaluated the impact of headaches in school, home, play, and social activities, is comprised of six items that pertain to days missed in various activities over the past 90 days. Questions were answered by the youth in consultation with their parents and reviewed by study staff. The PedMIDAS scale was administered at baseline (covering the three months prior to enrollment) and at the 24-week endpoint visit (the end of the maintenance period, covering three months of enrollment). A total PedMIDAS score (sum of items 1-6) was used in this trial. Scores range from 0-240; with a score of 0-10 indicating no disability, 11-30 mild disability, 31-50 moderate disability, and more than 50 severe disability in daily activities. The main outcome measure for this comparison will be the difference in the baseline and endpoint (24 week) PedMIDAS total scores for:

  1. Amitriptyline vs. Placebo
  2. Topiramate vs. Placebo
  3. Amitriptyline vs Topiramate
baseline and 24 week endpoint
Change in Number of Headache Days
Time Frame: 4 week baseline period and last 4 weeks of the 24-week trial

This outcomes measure examines whether the rate of absolute number of headache days, per 28 day period, differs between treatment groups over time. This was assessed longitudinally based on the actual number of headache days from the 28 days prior to randomization to the last 28 days of this 24 week trial. The change in absolute headache days was compared between:

  1. Amitriptyline vs. placebo
  2. Topiramate vs. placebo
  3. Amitriptyline vs. Topiramate
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
Time Frame: 24 weeks
To assess tolerability, the percentage of subjects who complete the entire 24-week treatment period will be estimated in each of the three groups.
24 weeks
Occurrence of Treatment Emergent Serious Adverse Events
Time Frame: 24 weeks of the trial
To determine if amitriptyline or topiramate differ from placebo on the occurrence of treatment emergent serious adverse events.
24 weeks of the trial

Collaborators and Investigators

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

Sponsor

Children's Hospital Medical Center, Cincinnati

Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

  • Principal Investigator: 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

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

June 1, 2012

Primary Completion (ACTUAL)

April 1, 2015

Study Completion (ACTUAL)

January 1, 2016

Study Registration Dates

First Submitted

December 16, 2011

First Submitted That Met QC Criteria

April 18, 2012

First Posted (ESTIMATE)

April 20, 2012

Study Record Updates

Last Update Posted (ACTUAL)

August 10, 2017

Last Update Submitted That Met QC Criteria

July 11, 2017

Last Verified

July 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CIN-001
  • 1U01NS076788-01 (NIH)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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

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.

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