The Childhood and Adolescent Migraine Prevention Study
- Conditions
- MigraineMigraine DisordersHeadache
- Interventions
- Registration Number
- NCT01581281
- Lead Sponsor
- Children's Hospital Medical Center, Cincinnati
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 488
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Migraine with or without aura (International Classification of Headache Disorders, 2nd Edition (ICHD-II) or chronic migraine (ICHD-II revised)
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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)
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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
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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.
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Continuous migraine defined as an unrelenting headache for a 28 day period
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Weight less than 30 kg or greater than 120 kg
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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
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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
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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)
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Current use of disallowed medications/products: opioids, antipsychotics, antimanics, barbiturates, benzodiazepines, muscle relaxants, sedatives, tramadol, nutraceuticals, SSRIs, or SSNRIs
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Known history of allergic reaction or anaphylaxis to AMI or TPM
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Abnormal findings on ECG at baseline, particularly lengthening of the QT interval greater than or equal to 450 msec
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Subject is pregnant or has a positive pregnancy test
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Subject is sexually active and not using a medically acceptable form of contraception
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Diagnosis of epilepsy or other neurological diseases
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History of kidney stones
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Inability to swallow pills after using behavioral techniques if indicated between screening visit and baseline visit (3)
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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
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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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Amitriptyline Amitriptyline Drug to be administered twice daily. Topiramate Topiramate Drug to be administered twice daily. Placebo Placebo To be administered twice daily.
- Primary Outcome Measures
Name Time Method Number (Percentage) of Participants Reporting a ≥ 50% Reduction in Headache Days 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.
- Secondary Outcome Measures
Name Time Method Change in Absolute Headache Disability Score on PedMIDAS 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 TopiramateChange in Number of Headache Days 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. TopiramateTolerability, as Indicated by the Number (Percentage) of Participants That Completed the 24-week Treatment Phase 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.
Occurrence of Treatment Emergent Serious Adverse Events 24 weeks of the trial To determine if amitriptyline or topiramate differ from placebo on the occurrence of treatment emergent serious adverse events.
Trial Locations
- Locations (35)
University of Maryland School of Medicine
🇺🇸Baltimore, Maryland, United States
University of Nevada
🇺🇸Reno, Nevada, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Preferred Clinical Research
🇺🇸Pittsburgh, Pennsylvania, United States
Josephson Wallack Munshower Neurology Research
🇺🇸Indianapolis, Indiana, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Eastern Virginia Medical School
🇺🇸Norfolk, Virginia, United States
Phoenix Children's Medical Group
🇺🇸Phoenix, Arizona, United States
University of California-San Francisco Headache Center
🇺🇸San Francisco, California, United States
Premiere Research Institute
🇺🇸West Palm Beach, Florida, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Dent Neurological Institute
🇺🇸Amherst, New York, United States
University of Louisville Health Sciences Center
🇺🇸Louisville, Kentucky, United States
Children's Hospital of Boston
🇺🇸Waltham, Massachusetts, United States
Children's Mercy Hospital
🇺🇸Kansas City, Kansas, United States
Colorado Springs Neurological Associates
🇺🇸Colorado Springs, Colorado, United States
Akron Children's Hospital
🇺🇸Akron, Ohio, United States
Stanford Hospital and Clinics
🇺🇸Stanford, California, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Dallas Pediatric Neurology Associates
🇺🇸Dallas, Texas, United States
Saint Louis University
🇺🇸Saint Louis, Missouri, United States
Oklahoma Health Sciences
🇺🇸Oklahoma City, Oklahoma, United States
Marshfield Clinic
🇺🇸Marshfield, Wisconsin, United States
Primary Children's Medical Center
🇺🇸Salt Lake City, Utah, United States
Children's National Medical Center
🇺🇸Washington, D.C., District of Columbia, United States
Atlanta Headache Specialists
🇺🇸Atlanta, Georgia, United States
New England Regional Headache Center
🇺🇸Worcester, Massachusetts, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
The Headache Institute at Roosevelt Hospital
🇺🇸New York, New York, United States
Winthrop University Hospital
🇺🇸Mineola, New York, United States
Schenectady Neurological Constultants, PC
🇺🇸Schenectady, New York, United States
The Children's Hospital, Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
LeBonheur Children's Hospital
🇺🇸Memphis, Tennessee, United States
Scott and White Healthcare
🇺🇸Temple, Texas, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States