The Childhood and Adolescent Migraine Prevention Study

NCT ID: NCT01581281

Last Updated: 2017-08-10

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

488 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-06-30

Study Completion Date

2016-01-31

Brief Summary

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

Detailed Description

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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.

Conditions

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Migraine Migraine Disorders Headache

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Amitriptyline

Drug to be administered twice daily.

Group Type ACTIVE_COMPARATOR

Amitriptyline

Intervention Type DRUG

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.

Topiramate

Drug to be administered twice daily.

Group Type ACTIVE_COMPARATOR

Topiramate

Intervention Type DRUG

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

To be administered twice daily.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

Placebo

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

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

8 Years

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

Children's Hospital Medical Center, Cincinnati

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Scott W. Powers, PhD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital Medical Center, Cincinnati

Andrew D. Hershey, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital Medical Center, Cincinnati

Christopher S. Coffey, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Iowa

Locations

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Phoenix Children's Medical Group

Phoenix, Arizona, United States

Site Status

University of California-San Francisco Headache Center

San Francisco, California, United States

Site Status

Stanford Hospital and Clinics

Stanford, California, United States

Site Status

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status

Colorado Springs Neurological Associates

Colorado Springs, Colorado, United States

Site Status

Children's National Medical Center

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

Site Status

Premiere Research Institute

West Palm Beach, Florida, United States

Site Status

Atlanta Headache Specialists

Atlanta, Georgia, United States

Site Status

Josephson Wallack Munshower Neurology Research

Indianapolis, Indiana, United States

Site Status

Children's Mercy Hospital

Kansas City, Kansas, United States

Site Status

University of Louisville Health Sciences Center

Louisville, Kentucky, United States

Site Status

University of Maryland School of Medicine

Baltimore, Maryland, United States

Site Status

Children's Hospital of Boston

Waltham, Massachusetts, United States

Site Status

New England Regional Headache Center

Worcester, Massachusetts, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Saint Louis University

St Louis, Missouri, United States

Site Status

University of Nevada

Reno, Nevada, United States

Site Status

Dent Neurological Institute

Amherst, New York, United States

Site Status

Winthrop University Hospital

Mineola, New York, United States

Site Status

The Headache Institute at Roosevelt Hospital

New York, New York, United States

Site Status

Schenectady Neurological Constultants, PC

Schenectady, New York, United States

Site Status

Akron Children's Hospital

Akron, Ohio, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

The Children's Hospital, Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

Oklahoma Health Sciences

Oklahoma City, Oklahoma, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Preferred Clinical Research

Pittsburgh, Pennsylvania, United States

Site Status

LeBonheur Children's Hospital

Memphis, Tennessee, United States

Site Status

Dallas Pediatric Neurology Associates

Dallas, Texas, United States

Site Status

Scott and White Healthcare

Temple, Texas, United States

Site Status

Primary Children's Medical Center

Salt Lake City, Utah, United States

Site Status

Eastern Virginia Medical School

Norfolk, Virginia, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

Marshfield Clinic

Marshfield, Wisconsin, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 34865085 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34404270 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27788026 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23594025 (View on PubMed)

Other Identifiers

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1U01NS076788-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CIN-001

Identifier Type: -

Identifier Source: org_study_id

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