The Childhood and Adolescent Migraine Prevention Study
Condition: Migraine; Migraine Disorders; Headache
MeSH terms: Migraine Disorders; Headache
Intervention: Amitriptyline; Topiramate; Placebo
Intervention description: 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 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 will be administered twice daily at home during the 8-week titration period followed by a 16 week maintenance period.
Intervention MeSH terms: Topiramate; Amitriptyline
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 488.0
Sex: All
Minimum age: 8 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Pediatric; Children; Adolescent; Headache; Migraine

Summary:

      The purpose of this research study is to test two medicines for migraine prevention 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.