Clinical trial NCT01581281: The Childhood and Adolescent Migraine Prevention Study
Official title: Amitriptyline and Topiramate in the Prevention of Childhood Migraine
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Migraine
Migraine Disorders
Headache
Keywords: Pediatric
Children
Adolescent
Headache
Migraine
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2012-04-20
Enrollment: 488
Sex: ALL
Minimum age (years): 8
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number (Percentage) of Participants Reporting a ≥ 50% Reduction in Headache Days
timeFrame: 4 week baseline period and last 4 weeks of the 24-week trial
Secondary outcomes:
measure: Change in Absolute Headache Disability Score on PedMIDAS
timeFrame: baseline and 24 week endpoint
measure: Change in Number of Headache Days
timeFrame: 4 week baseline period and last 4 weeks of the 24-week trial
measure: Tolerability, as Indicated by the Number (Percentage) of Participants That Completed the 24-week Treatment Phase
timeFrame: 24 weeks
measure: Occurrence of Treatment Emergent Serious Adverse Events
timeFrame: 24 weeks of the trial
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Medical Group
state: Arizona
city: San Francisco
country: United States
facility: University of California-San Francisco Headache Center
state: California
city: Stanford
country: United States
facility: Stanford Hospital and Clinics
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Colorado Springs
country: United States
facility: Colorado Springs Neurological Associates
state: Colorado
city: Washington, D.C.
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: West Palm Beach
country: United States
facility: Premiere Research Institute
state: Florida
city: Atlanta
country: United States
facility: Atlanta Headache Specialists
state: Georgia
city: Indianapolis
country: United States
facility: Josephson Wallack Munshower Neurology Research
state: Indiana
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Kansas
city: Louisville
country: United States
facility: University of Louisville Health Sciences Center
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland School of Medicine
state: Maryland
city: Waltham
country: United States
facility: Children's Hospital of Boston
state: Massachusetts
city: Worcester
country: United States
facility: New England Regional Headache Center
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Reno
country: United States
facility: University of Nevada
state: Nevada
city: Amherst
country: United States
facility: Dent Neurological Institute
state: New York
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: New York
country: United States
facility: The Headache Institute at Roosevelt Hospital
state: New York
city: Schenectady
country: United States
facility: Schenectady Neurological Constultants, PC
state: New York
city: Akron
country: United States
facility: Akron Children's Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: The Children's Hospital, Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Health Sciences
state: Oklahoma
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Preferred Clinical Research
state: Pennsylvania
city: Memphis
country: United States
facility: LeBonheur Children's Hospital
state: Tennessee
city: Dallas
country: United States
facility: Dallas Pediatric Neurology Associates
state: Texas
city: Temple
country: United States
facility: Scott and White Healthcare
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Medical Center
state: Utah
city: Norfolk
country: United States
facility: Eastern Virginia Medical School
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Marshfield
country: United States
facility: Marshfield Clinic
state: Wisconsin
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Scott W. Powers, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital Medical Center, Cincinnati
name: Andrew D. Hershey, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Iowa
name: Christopher S. Coffey, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.