The purpose of this research study is to test two medicines for migraine prevention in children and adolescents.
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
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
488
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.
Number (Percentage) of Participants Reporting a ≥ 50% Reduction in Headache Days
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.
Time frame: 4 week baseline period and last 4 weeks of the 24-week trial
Change in Absolute Headache Disability Score on PedMIDAS
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
Time frame: baseline and 24 week endpoint
Change in Number of Headache Days
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
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Phoenix Children's Medical Group
Phoenix, Arizona, United States
University of California-San Francisco Headache Center
San Francisco, California, United States
Stanford Hospital and Clinics
Stanford, California, United States
Children's Hospital Colorado
Aurora, Colorado, United States
Colorado Springs Neurological Associates
Colorado Springs, Colorado, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Premiere Research Institute
West Palm Beach, Florida, United States
Atlanta Headache Specialists
Atlanta, Georgia, United States
Josephson Wallack Munshower Neurology Research
Indianapolis, Indiana, United States
Children's Mercy Hospital
Kansas City, Kansas, United States
...and 25 more locations
Time frame: 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
To assess tolerability, the percentage of subjects who complete the entire 24-week treatment period will be estimated in each of the three groups.
Time frame: 24 weeks
Occurrence of Treatment Emergent Serious Adverse Events
To determine if amitriptyline or topiramate differ from placebo on the occurrence of treatment emergent serious adverse events.
Time frame: 24 weeks of the trial