{"protocolSection":{"identificationModule":{"nctId":"NCT01581281","orgStudyIdInfo":{"id":"CIN-001"},"secondaryIdInfos":[{"id":"1U01NS076788-01","type":"NIH","link":"https://reporter.nih.gov/quickSearch/1U01NS076788-01"}],"organization":{"fullName":"Children's Hospital Medical Center, Cincinnati","class":"OTHER"},"briefTitle":"The Childhood and Adolescent Migraine Prevention Study","officialTitle":"Amitriptyline and Topiramate in the Prevention of Childhood Migraine","acronym":"CHAMP"},"statusModule":{"statusVerifiedDate":"2017-07","overallStatus":"TERMINATED","whyStopped":"Interim assessment provided sufficient data to answer study questions","expandedAccessInfo":{"hasExpandedAccess":false},"startDateStruct":{"date":"2012-06"},"primaryCompletionDateStruct":{"date":"2015-04","type":"ACTUAL"},"completionDateStruct":{"date":"2016-01","type":"ACTUAL"},"studyFirstSubmitDate":"2011-12-16","studyFirstSubmitQcDate":"2012-04-18","studyFirstPostDateStruct":{"date":"2012-04-20","type":"ESTIMATED"},"resultsFirstSubmitDate":"2016-11-16","resultsFirstSubmitQcDate":"2017-07-11","resultsFirstPostDateStruct":{"date":"2017-08-10","type":"ACTUAL"},"lastUpdateSubmitDate":"2017-07-11","lastUpdatePostDateStruct":{"date":"2017-08-10","type":"ACTUAL"}},"sponsorCollaboratorsModule":{"responsibleParty":{"type":"SPONSOR"},"leadSponsor":{"name":"Children's Hospital Medical Center, Cincinnati","class":"OTHER"},"collaborators":[{"name":"National Institute of Neurological Disorders and Stroke (NINDS)","class":"NIH"}]},"oversightModule":{"oversightHasDmc":true},"descriptionModule":{"briefSummary":"The purpose of this research study is to test two medicines for migraine prevention in children and adolescents.","detailedDescription":"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."},"conditionsModule":{"conditions":["Migraine","Migraine Disorders","Headache"],"keywords":["Pediatric","Children","Adolescent","Headache","Migraine"]},"designModule":{"studyType":"INTERVENTIONAL","phases":["PHASE3"],"designInfo":{"allocation":"RANDOMIZED","interventionModel":"PARALLEL","primaryPurpose":"PREVENTION","maskingInfo":{"masking":"QUADRUPLE","whoMasked":["PARTICIPANT","CARE_PROVIDER","INVESTIGATOR","OUTCOMES_ASSESSOR"]}},"enrollmentInfo":{"count":488,"type":"ACTUAL"}},"armsInterventionsModule":{"armGroups":[{"label":"Amitriptyline","type":"ACTIVE_COMPARATOR","description":"Drug to be administered twice daily.","interventionNames":["Drug: Amitriptyline"]},{"label":"Topiramate","type":"ACTIVE_COMPARATOR","description":"Drug to be administered twice daily.","interventionNames":["Drug: Topiramate"]},{"label":"Placebo","type":"PLACEBO_COMPARATOR","description":"To be administered twice daily.","interventionNames":["Drug: Placebo"]}],"interventions":[{"type":"DRUG","name":"Amitriptyline","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.","armGroupLabels":["Amitriptyline"]},{"type":"DRUG","name":"Topiramate","description":"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.","armGroupLabels":["Topiramate"]},{"type":"DRUG","name":"Placebo","description":"Placebo will be administered twice daily at home during the 8-week titration period followed by a 16 week maintenance period.","armGroupLabels":["Placebo"]}]},"outcomesModule":{"primaryOutcomes":[{"measure":"Number (Percentage) of Participants Reporting a ≥ 50% Reduction in Headache Days","description":"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.\n\nFor 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.","timeFrame":"4 week baseline period and last 4 weeks of the 24-week trial"}],"secondaryOutcomes":[{"measure":"Change in Absolute Headache Disability Score on PedMIDAS","description":"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:\n\n1. Amitriptyline vs. Placebo\n2. Topiramate vs. Placebo\n3. Amitriptyline vs Topiramate","timeFrame":"baseline and 24 week endpoint"},{"measure":"Change in Number of Headache Days","description":"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:\n\n1. Amitriptyline vs. placebo\n2. Topiramate vs. placebo\n3. Amitriptyline vs. Topiramate","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","description":"To assess tolerability, the percentage of subjects who complete the entire 24-week treatment period will be estimated in each of the three groups.","timeFrame":"24 weeks"},{"measure":"Occurrence of Treatment Emergent Serious Adverse Events","description":"To determine if amitriptyline or topiramate differ from placebo on the occurrence of treatment emergent serious adverse events.","timeFrame":"24 weeks of the trial"}]},"eligibilityModule":{"eligibilityCriteria":"Inclusion Criteria:\n\n* Migraine with or without aura (International Classification of Headache Disorders, 2nd Edition (ICHD-II) or chronic migraine (ICHD-II revised)\n* 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)\n* 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\n* Females or males 8-17 years, inclusive\n\n  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.\n\nExclusion Criteria:\n\n* Continuous migraine defined as an unrelenting headache for a 28 day period\n* Weight less than 30 kg or greater than 120 kg\n* 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\n* 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\n* 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)\n* Current use of disallowed medications/products: opioids, antipsychotics, antimanics, barbiturates, benzodiazepines, muscle relaxants, sedatives, tramadol, nutraceuticals, SSRIs, or SSNRIs\n* Known history of allergic reaction or anaphylaxis to AMI or TPM\n* Abnormal findings on ECG at baseline, particularly lengthening of the QT interval greater than or equal to 450 msec\n* Subject is pregnant or has a positive pregnancy test\n* Subject is sexually active and not using a medically acceptable form of contraception\n* Diagnosis of epilepsy or other neurological diseases\n* History of kidney stones\n* Inability to swallow pills after using behavioral techniques if indicated between screening visit and baseline visit (3)\n* 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\n* 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\n\n  (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.\n\n  (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.","healthyVolunteers":false,"sex":"ALL","minimumAge":"8 Years","maximumAge":"17 Years","stdAges":["CHILD"]},"contactsLocationsModule":{"overallOfficials":[{"name":"Scott W. Powers, PhD","affiliation":"Children's Hospital Medical Center, Cincinnati","role":"PRINCIPAL_INVESTIGATOR"},{"name":"Andrew D. Hershey, MD, PhD","affiliation":"Children's Hospital Medical Center, Cincinnati","role":"PRINCIPAL_INVESTIGATOR"},{"name":"Christopher S. Coffey, PhD","affiliation":"University of Iowa","role":"PRINCIPAL_INVESTIGATOR"}],"locations":[{"facility":"Phoenix Children's Medical Group","city":"Phoenix","state":"Arizona","zip":"85016","country":"United States","geoPoint":{"lat":33.44838,"lon":-112.07404}},{"facility":"University of California-San Francisco Headache Center","city":"San Francisco","state":"California","zip":"94115","country":"United States","geoPoint":{"lat":37.77493,"lon":-122.41942}},{"facility":"Stanford Hospital and Clinics","city":"Stanford","state":"California","zip":"94305","country":"United States","geoPoint":{"lat":37.42411,"lon":-122.16608}},{"facility":"Children's Hospital Colorado","city":"Aurora","state":"Colorado","zip":"80045","country":"United States","geoPoint":{"lat":39.72943,"lon":-104.83192}},{"facility":"Colorado Springs Neurological Associates","city":"Colorado Springs","state":"Colorado","zip":"80907","country":"United States","geoPoint":{"lat":38.83388,"lon":-104.82136}},{"facility":"Children's National Medical Center","city":"Washington D.C.","state":"District of Columbia","zip":"20010","country":"United States","geoPoint":{"lat":38.89511,"lon":-77.03637}},{"facility":"Premiere Research Institute","city":"West Palm Beach","state":"Florida","zip":"33407","country":"United States","geoPoint":{"lat":26.71534,"lon":-80.05337}},{"facility":"Atlanta Headache Specialists","city":"Atlanta","state":"Georgia","zip":"30342","country":"United States","geoPoint":{"lat":33.749,"lon":-84.38798}},{"facility":"Josephson Wallack Munshower Neurology Research","city":"Indianapolis","state":"Indiana","zip":"46237","country":"United States","geoPoint":{"lat":39.76838,"lon":-86.15804}},{"facility":"Children's Mercy Hospital","city":"Kansas City","state":"Kansas","zip":"66160","country":"United States","geoPoint":{"lat":39.11417,"lon":-94.62746}},{"facility":"University of Louisville Health Sciences Center","city":"Louisville","state":"Kentucky","zip":"40292","country":"United States","geoPoint":{"lat":38.25424,"lon":-85.75941}},{"facility":"University of Maryland School of Medicine","city":"Baltimore","state":"Maryland","zip":"21201","country":"United States","geoPoint":{"lat":39.29038,"lon":-76.61219}},{"facility":"Children's Hospital of Boston","city":"Waltham","state":"Massachusetts","zip":"02453","country":"United States","geoPoint":{"lat":42.37649,"lon":-71.23561}},{"facility":"New England Regional Headache Center","city":"Worcester","state":"Massachusetts","zip":"01605","country":"United States","geoPoint":{"lat":42.26259,"lon":-71.80229}},{"facility":"Mayo Clinic","city":"Rochester","state":"Minnesota","zip":"55905","country":"United States","geoPoint":{"lat":44.02163,"lon":-92.4699}},{"facility":"Saint Louis University","city":"St Louis","state":"Missouri","zip":"63104","country":"United States","geoPoint":{"lat":38.62727,"lon":-90.19789}},{"facility":"University of Nevada","city":"Reno","state":"Nevada","zip":"89502","country":"United States","geoPoint":{"lat":39.52963,"lon":-119.8138}},{"facility":"Dent Neurological Institute","city":"Amherst","state":"New York","zip":"14226","country":"United States","geoPoint":{"lat":42.97839,"lon":-78.79976}},{"facility":"Winthrop University Hospital","city":"Mineola","state":"New York","zip":"11501","country":"United States","geoPoint":{"lat":40.74927,"lon":-73.64068}},{"facility":"The Headache Institute at Roosevelt Hospital","city":"New York","state":"New York","zip":"10019","country":"United States","geoPoint":{"lat":40.71427,"lon":-74.00597}},{"facility":"Schenectady Neurological Constultants, PC","city":"Schenectady","state":"New York","zip":"12308","country":"United States","geoPoint":{"lat":42.81424,"lon":-73.93957}},{"facility":"Akron Children's Hospital","city":"Akron","state":"Ohio","zip":"44308","country":"United States","geoPoint":{"lat":41.08144,"lon":-81.51901}},{"facility":"Cincinnati Children's Hospital Medical Center","city":"Cincinnati","state":"Ohio","zip":"45229","country":"United States","geoPoint":{"lat":39.12711,"lon":-84.51439}},{"facility":"The Children's Hospital, Cleveland Clinic","city":"Cleveland","state":"Ohio","zip":"44195","country":"United States","geoPoint":{"lat":41.4995,"lon":-81.69541}},{"facility":"Nationwide Children's Hospital","city":"Columbus","state":"Ohio","zip":"43205","country":"United States","geoPoint":{"lat":39.96118,"lon":-82.99879}},{"facility":"Oklahoma Health Sciences","city":"Oklahoma City","state":"Oklahoma","zip":"73104","country":"United States","geoPoint":{"lat":35.46756,"lon":-97.51643}},{"facility":"Children's Hospital of Philadelphia","city":"Philadelphia","state":"Pennsylvania","zip":"19104","country":"United States","geoPoint":{"lat":39.95238,"lon":-75.16362}},{"facility":"Preferred Clinical Research","city":"Pittsburgh","state":"Pennsylvania","zip":"15236","country":"United States","geoPoint":{"lat":40.44062,"lon":-79.99589}},{"facility":"LeBonheur Children's Hospital","city":"Memphis","state":"Tennessee","zip":"38105","country":"United States","geoPoint":{"lat":35.14953,"lon":-90.04898}},{"facility":"Dallas Pediatric Neurology Associates","city":"Dallas","state":"Texas","zip":"75230","country":"United States","geoPoint":{"lat":32.78306,"lon":-96.80667}},{"facility":"Scott and White Healthcare","city":"Temple","state":"Texas","zip":"76508","country":"United States","geoPoint":{"lat":31.09823,"lon":-97.34278}},{"facility":"Primary Children's Medical Center","city":"Salt Lake City","state":"Utah","zip":"84108","country":"United States","geoPoint":{"lat":40.76078,"lon":-111.89105}},{"facility":"Eastern Virginia Medical School","city":"Norfolk","state":"Virginia","zip":"23510","country":"United States","geoPoint":{"lat":36.84681,"lon":-76.28522}},{"facility":"Seattle Children's Hospital","city":"Seattle","state":"Washington","zip":"98105","country":"United States","geoPoint":{"lat":47.60621,"lon":-122.33207}},{"facility":"Marshfield Clinic","city":"Marshfield","state":"Wisconsin","zip":"54449","country":"United States","geoPoint":{"lat":44.66885,"lon":-90.1718}}]},"referencesModule":{"references":[{"pmid":"34865085","type":"DERIVED","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."},{"pmid":"34404270","type":"DERIVED","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."},{"pmid":"27788026","type":"DERIVED","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."},{"pmid":"23594025","type":"DERIVED","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."}]},"ipdSharingStatementModule":{"ipdSharing":"YES","description":"De-identified datasets and associated documentation will be submitted to NINDS for archiving and public access, consistent with current NINDS data sharing policy."}},"resultsSection":{"participantFlowModule":{"preAssignmentDetails":"Of the patients assessed for eligibility, 21 (4%) did not undergo randomization owing to early trial closure and 106 (22%) were excluded. Eighty-one (81) were excluded due to not meeting inclusion criteria, 25 declined participation (13 were unwilling, but eligibility was otherwise confirmed and 12 were willing and eligibility was unknown).","recruitmentDetails":"From July 16, 2012 through November 24, 2014, 488 patients were assessed for eligibility from 31 sites in the United States. Of those, 361 patients underwent randomization.","groups":[{"id":"FG000","title":"Topiramate","description":"Topiramate enclosed in capsules to maintain the blind was administered orally in a divided dose of 1 capsule twice daily. A target dose was 2 mg per kilogram per day. Dose escalation occurred every two weeks over a period of 8 weeks, with dose modification based on side effects. A 16 week constant-dose (maintenance) phase followed at the highest dosage achieved."},{"id":"FG001","title":"Placebo","description":"Placebo enclosed in capsules to maintain the blind was administered orally twice daily during an 8 week titration period followed by a 16 week maintenance phase (mirroring the other two treatment arms)."},{"id":"FG002","title":"Amitriptyline","description":"Amitriptyline enclosed in capsules to maintain the blind was administered orally in dose of 1 capsule twice daily (AM capsule did not contain medication. A target dose was 1 mg per kilogram per day. Dose escalation occurred every two weeks over a period of 8 weeks, with dose modification based on side effects. A 16 week constant-dose (maintenance) phase followed at the highest dosage achieved."}],"periods":[{"title":"Overall Study","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"145"},{"groupId":"FG001","numSubjects":"72"},{"groupId":"FG002","numSubjects":"144"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"130"},{"groupId":"FG001","numSubjects":"66"},{"groupId":"FG002","numSubjects":"132"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"15"},{"groupId":"FG001","numSubjects":"6"},{"groupId":"FG002","numSubjects":"12"}]}],"dropWithdraws":[{"type":"Early Study Closure","reasons":[{"groupId":"FG000","numSubjects":"15"},{"groupId":"FG001","numSubjects":"6"},{"groupId":"FG002","numSubjects":"12"}]}]}]},"baselineCharacteristicsModule":{"groups":[{"id":"BG000","title":"Topiramate","description":"Topiramate enclosed in capsules to maintain the blind was administered orally in a divided dose of 1 capsule twice daily. A target dose was 2 mg per kilogram per day. Dose escalation occurred every two weeks over a period of 8 weeks, with dose modification based on side effects. A 16 week constant-dose (maintenance) phase followed at the highest dosage achieved."},{"id":"BG001","title":"Placebo","description":"Placebo enclosed in capsules to maintain the blind was administered orally twice daily during an 8 week titration period followed by a 16 week maintenance phase (mirroring the other two treatment arms)."},{"id":"BG002","title":"Amitriptyline","description":"Amitriptyline enclosed in capsules to maintain the blind was administered orally in dose of 1 capsule twice daily (AM capsule did not contain medication. A target dose was 1 mg per kilogram per day. Dose escalation occurred every two weeks over a period of 8 weeks, with dose modification based on side effects. A 16 week constant-dose (maintenance) phase followed at the highest dosage achieved."},{"id":"BG003","title":"Total","description":"Total of all reporting groups"}],"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"145"},{"groupId":"BG001","value":"72"},{"groupId":"BG002","value":"144"},{"groupId":"BG003","value":"361"}]}],"measures":[{"title":"Age, Categorical","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"<=18 years","measurements":[{"groupId":"BG000","value":"145"},{"groupId":"BG001","value":"72"},{"groupId":"BG002","value":"144"},{"groupId":"BG003","value":"361"}]},{"title":"Between 18 and 65 years","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"},{"groupId":"BG003","value":"0"}]},{"title":">=65 years","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"},{"groupId":"BG003","value":"0"}]}]}]},{"title":"Age, Continuous","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"years","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"14.2","spread":"2.5"},{"groupId":"BG001","value":"14.2","spread":"2.2"},{"groupId":"BG002","value":"14.2","spread":"2.4"},{"groupId":"BG003","value":"14.2","spread":"2.4"}]}]}]},{"title":"Sex: Female, Male","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"Female","measurements":[{"groupId":"BG000","value":"101"},{"groupId":"BG001","value":"49"},{"groupId":"BG002","value":"97"},{"groupId":"BG003","value":"247"}]},{"title":"Male","measurements":[{"groupId":"BG000","value":"44"},{"groupId":"BG001","value":"23"},{"groupId":"BG002","value":"47"},{"groupId":"BG003","value":"114"}]}]}]},{"title":"Ethnicity (NIH/OMB)","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"Hispanic or Latino","measurements":[{"groupId":"BG000","value":"14"},{"groupId":"BG001","value":"6"},{"groupId":"BG002","value":"8"},{"groupId":"BG003","value":"28"}]},{"title":"Not Hispanic or Latino","measurements":[{"groupId":"BG000","value":"123"},{"groupId":"BG001","value":"65"},{"groupId":"BG002","value":"128"},{"groupId":"BG003","value":"316"}]},{"title":"Unknown or Not Reported","measurements":[{"groupId":"BG000","value":"8"},{"groupId":"BG001","value":"1"},{"groupId":"BG002","value":"8"},{"groupId":"BG003","value":"17"}]}]}]},{"title":"Race (NIH/OMB)","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"American Indian or Alaska Native","measurements":[{"groupId":"BG000","value":"14"},{"groupId":"BG001","value":"5"},{"groupId":"BG002","value":"8"},{"groupId":"BG003","value":"27"}]},{"title":"Asian","measurements":[{"groupId":"BG000","value":"6"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"},{"groupId":"BG003","value":"6"}]},{"title":"Native Hawaiian or Other Pacific Islander","measurements":[{"groupId":"BG000","value":"1"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"},{"groupId":"BG003","value":"1"}]},{"title":"Black or African American","measurements":[{"groupId":"BG000","value":"24"},{"groupId":"BG001","value":"17"},{"groupId":"BG002","value":"26"},{"groupId":"BG003","value":"67"}]},{"title":"White","measurements":[{"groupId":"BG000","value":"98"},{"groupId":"BG001","value":"48"},{"groupId":"BG002","value":"107"},{"groupId":"BG003","value":"253"}]},{"title":"More than one race","measurements":[{"groupId":"BG000","value":"NA","comment":"data not collected"},{"groupId":"BG001","value":"NA","comment":"data not collected"},{"groupId":"BG002","value":"NA","comment":"data not collected"},{"groupId":"BG003","value":"NA","comment":"Total not calculated because data are not available (NA) in one or more arms."}]},{"title":"Unknown or Not Reported","measurements":[{"groupId":"BG000","value":"2"},{"groupId":"BG001","value":"2"},{"groupId":"BG002","value":"3"},{"groupId":"BG003","value":"7"}]}]}]},{"title":"Region of Enrollment","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"title":"United States","categories":[{"measurements":[{"groupId":"BG000","value":"145"},{"groupId":"BG001","value":"72"},{"groupId":"BG002","value":"144"},{"groupId":"BG003","value":"361"}]}]}]},{"title":"Headache Days","description":"Number of headache days during 28-day baseline period","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"days","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"11.5","spread":"6.1"},{"groupId":"BG001","value":"11.0","spread":"6.3"},{"groupId":"BG002","value":"11.5","spread":"6.2"},{"groupId":"BG003","value":"11.4","spread":"6.1"}]}]}]},{"title":"Pediatric Migriane Disability Assessment Score (PedMIDAS)","description":"Scores on the PedMIDAS range from 0 to 240, with a score of 1 to 10 indicating no disability, 11 to 30 indicating mild disability, 31 to 50 indicating moderate disability, and more than 50 indicating severe disability.","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"units on a scale","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"42.6","spread":"27.4"},{"groupId":"BG001","value":"42.9","spread":"26.7"},{"groupId":"BG002","value":"40.6","spread":"26.4"},{"groupId":"BG003","value":"41.9","spread":"26.8"}]}]}]}]},"outcomeMeasuresModule":{"outcomeMeasures":[{"type":"PRIMARY","title":"Number (Percentage) of Participants Reporting a ≥ 50% Reduction in Headache Days","description":"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.\n\nFor 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.","populationDescription":"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 between the participants receiving amitriptyline and participants receiving placebo.","reportingStatus":"POSTED","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","timeFrame":"4 week baseline period and last 4 weeks of the 24-week trial","groups":[{"id":"OG000","title":"Topiramate","description":"Topiramate enclosed in capsules to maintain the blind was administered orally in a divided dose of 1 capsule twice daily. A target dose was 2 mg per kilogram per day. Dose escalation occurred every two weeks over a period of 8 weeks, with dose modification based on side effects. A 16 week constant-dose (maintenance) phase followed at the highest dosage achieved"},{"id":"OG001","title":"Placebo","description":"Placebo enclosed in capsules to maintain the blind was administered orally twice daily during an 8 week titration period followed by a 16 week maintenance phase (mirroring the other two treatment arms)."},{"id":"OG002","title":"Amitriptyline","description":"Amitriptyline enclosed in capsules to maintain the blind was administered orally in dose of 1 capsule twice daily (AM capsule did not contain medication. A target dose was 1 mg per kilogram per day. Dose escalation occurred every two weeks over a period of 8 weeks, with dose modification based on side effects. A 16 week constant-dose (maintenance) phase followed at the highest dosage achieved."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"130"},{"groupId":"OG001","value":"66"},{"groupId":"OG002","value":"132"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"72"},{"groupId":"OG001","value":"40"},{"groupId":"OG002","value":"69"}]}]}],"analyses":[{"groupIds":["OG001","OG002"],"groupDescription":"Logistic regression models were used to estimate the odds of successful primary endpoint for amitriptyline relative to placebo. The analyses followed the intention to treat principle, imputing an outcome of \"failure\" for any participant who withdrew early for any reason or did not provide week 24 headache diary data (endpoint data). The models, and corresponding odds ratios, were adjusted for the two stratification variables (age and baseline number of headache days).","nonInferiorityType":"SUPERIORITY","pValue":"0.2636","pValueComment":"A Bonferroni approach was used to control the type I error rate. Because there were three comparisons, the Bonferroni corrected level of significance is 0.017 (= 0.05 / 3).","statisticalMethod":"Regression, Logistic","paramType":"Odds Ratio (OR)","paramValue":"0.71","ciPctValue":"98.3","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.34","ciUpperLimit":"1.48"},{"groupIds":["OG000","OG001"],"groupDescription":"Logistic regression models were used to estimate the odds of successful primary endpoint for topiramate relative to placebo. The analyses followed the intention to treat principle, imputing an outcome of \"failure\" for any participant who withdrew early for any reason or did not provide week 24 headache diary data (endpoint data). The models, and corresponding odds ratios, were adjusted for the two stratification variables (age and baseline number of headache days).","nonInferiorityType":"SUPERIORITY","pValue":"0.4821","pValueComment":"A Bonferroni approach was used to control the type I error rate. Because there were three comparisons of interest, the Bonferroni corrected level of significance is 0.017 ( = 0.05 / 3).","statisticalMethod":"Regression, Logistic","paramType":"Odds Ratio (OR)","paramValue":"0.81","ciPctValue":"98.3","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.39","ciUpperLimit":"1.68"},{"groupIds":["OG000","OG002"],"groupDescription":"Logistic regression models were used to estimate the odds of successful primary endpoint for topiramate relative to amitriptyline. The analyses followed the intention to treat principle, imputing an outcome of \"failure\" for any participant who withdrew early for any reason or did not provide week 24 headache diary data (endpoint data). The models, and corresponding odds ratios, were adjusted for the two stratification variables (age and baseline number of headache days).","nonInferiorityType":"SUPERIORITY","pValue":"0.6107","pValueComment":"A Bonferroni approach was used to control the type I error rate. Because there were three comparisons of interest, the Bonferroni corrected level of significance is 0.017 ( = 0.05 / 3).","statisticalMethod":"Regression, Logistic","paramType":"Odds Ratio (OR)","paramValue":"0.88","ciPctValue":"98.3","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.49","ciUpperLimit":"1.59"}]},{"type":"SECONDARY","title":"Change in Absolute Headache Disability Score on PedMIDAS","description":"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:\n\n1. Amitriptyline vs. Placebo\n2. Topiramate vs. Placebo\n3. Amitriptyline vs Topiramate","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"Standard Deviation","unitOfMeasure":"units on a scale","timeFrame":"baseline and 24 week endpoint","groups":[{"id":"OG000","title":"Topiramate","description":"Topiramate enclosed in capsules to maintain the blind was administered orally in a divided dose of 1 capsule twice daily. A target dose was 2 mg per kilogram per day. Dose escalation occurred every two weeks over a period of 8 weeks, with dose modification based on side effects. A 16 week constant-dose (maintenance) phase followed at the highest dosage achieved."},{"id":"OG001","title":"Placebo","description":"Placebo enclosed in capsules to maintain the blind was administered orally twice daily during an 8 week titration period followed by a 16 week maintenance phase (mirroring the other two treatment arms)."},{"id":"OG002","title":"Amitriptyline","description":"Amitriptyline enclosed in capsules to maintain the blind was administered orally in dose of 1 capsule twice daily (AM capsule did not contain medication. A target dose was 1 mg per kilogram per day. Dose escalation occurred every two weeks over a period of 8 weeks, with dose modification based on side effects. A 16 week constant-dose (maintenance) phase followed at the highest dosage achieved."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"130"},{"groupId":"OG001","value":"66"},{"groupId":"OG002","value":"132"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"-26.8","spread":"27.5"},{"groupId":"OG001","value":"-22.6","spread":"29.42"},{"groupId":"OG002","value":"-22.5","spread":"26.37"}]}]}],"analyses":[{"groupIds":["OG001","OG002"],"groupDescription":"The mean change from baseline in PedMIDAS score over time for the three groups was assessed using a linear regression model for each of the three pairwise comparisons (Amitriptyline relative to placebo, Topiramate relative to placebo, and Amitriptyline relative to Topiramate), adjusted for the baseline PedMIDAS score. The models, and corresponding odds ratios, were adjusted for the two stratification variables (age and baseline number of headache days).","nonInferiorityType":"SUPERIORITY","pValue":"0.9137","statisticalMethod":"Regression, Linear","paramType":"Mean Difference (Final Values)","paramValue":"-0.35","ciPctValue":"95","ciNumSides":"TWO_SIDED","ciLowerLimit":"-6.64","ciUpperLimit":"5.95"},{"groupIds":["OG000","OG001"],"groupDescription":"The mean change from baseline in PedMIDAS score over time for the three groups was assessed using a linear regression model for each of the three pairwise comparisons (Amitriptyline relative to placebo, Topiramate relative to placebo, and Amitriptyline relative to Topiramate), adjusted for the baseline PedMIDAS score. The models, and corresponding odds ratios, were adjusted for the two stratification variables (age and baseline number of headache days).","nonInferiorityType":"SUPERIORITY","pValue":"0.1331","statisticalMethod":"Regression, Linear","paramType":"Median Difference (Final Values)","paramValue":"-4.84","ciPctValue":"95","ciNumSides":"TWO_SIDED","ciLowerLimit":"-11.16","ciUpperLimit":"1.49"},{"groupIds":["OG000","OG002"],"groupDescription":"The mean change from baseline in PedMIDAS score over time for the three groups was assessed using a linear regression model for each of the three pairwise comparisons (Amitriptyline relative to placebo, Topiramate relative to placebo, and Amitriptyline relative to Topiramate), adjusted for the baseline PedMIDAS score. The models, and corresponding odds ratios, were adjusted for the two stratification variables (age and baseline number of headache days).","nonInferiorityType":"SUPERIORITY","pValue":"0.1011","statisticalMethod":"Regression, Linear","paramType":"Mean Difference (Final Values)","paramValue":"4.49","ciPctValue":"95","ciNumSides":"TWO_SIDED","ciLowerLimit":"-0.88","ciUpperLimit":"9.87"}]},{"type":"SECONDARY","title":"Change in Number of Headache Days","description":"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:\n\n1. Amitriptyline vs. placebo\n2. Topiramate vs. placebo\n3. Amitriptyline vs. Topiramate","populationDescription":"The analysis population included all participants who had observed end-point data: 101 in the topiramate group, 59 in the placebo group, and104 in the amitriptyline group.","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"Standard Deviation","unitOfMeasure":"days","timeFrame":"4 week baseline period and last 4 weeks of the 24-week trial","groups":[{"id":"OG000","title":"Topiramate","description":"Topiramate enclosed in capsules to maintain the blind was administered orally in a divided dose of 1 capsule twice daily. A target dose was 2 mg per kilogram per day. Dose escalation occurred every two weeks over a period of 8 weeks, with dose modification based on side effects. A 16 week constant-dose (maintenance) phase followed at the highest dosage achieved."},{"id":"OG001","title":"Placebo","description":"Placebo enclosed in capsules to maintain the blind was administered orally twice daily during an 8 week titration period followed by a 16 week maintenance phase (mirroring the other two treatment arms)."},{"id":"OG002","title":"Amitriptyline","description":"Amitriptyline enclosed in capsules to maintain the blind was administered orally in dose of 1 capsule twice daily (AM capsule did not contain medication. A target dose was 1 mg per kilogram per day. Dose escalation occurred every two weeks over a period of 8 weeks, with dose modification based on side effects. A 16 week constant-dose (maintenance) phase followed at the highest dosage achieved."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"101"},{"groupId":"OG001","value":"59"},{"groupId":"OG002","value":"104"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"-6.7","spread":"4.99"},{"groupId":"OG001","value":"-5.9","spread":"6.96"},{"groupId":"OG002","value":"-6.7","spread":"6.20"}]}]}],"analyses":[{"groupIds":["OG001","OG002"],"groupDescription":"Another major secondary objective was to determine if the change in absolute headache days from baseline to week 24 differed between treatment groups. This objective was assessed using linear regression models, with three pairwise comparisons between treatment groups (Amitriptyline vs. Placebo, Topiramate vs. Placebo, and Amitriptyline vs. Topiramate). The models, and corresponding odds ratios, were adjusted for the two stratification variables (age and baseline number of headache days).","nonInferiorityType":"SUPERIORITY","pValue":"0.3553","pValueComment":"Each comparison was tested using a Bonferroni corrected significance level of 0.017 (0.05/3).","statisticalMethod":"Regression, Linear","paramType":"Mean Difference (Final Values)","paramValue":"-0.72","ciPctValue":"98.3","ciNumSides":"TWO_SIDED","ciLowerLimit":"-2.59","ciUpperLimit":"1.15"},{"groupIds":["OG000","OG001"],"groupDescription":"Another major secondary objective was to determine if the change in absolute headache days from baseline to week 24 differed between treatment groups. This objective was assessed using linear regression models, with three pairwise comparisons between treatment groups (Amitriptyline vs. Placebo, Topiramate vs. Placebo, and Amitriptyline vs. Topiramate). The models, and corresponding odds ratios, were adjusted for the two stratification variables (age and baseline number of headache days).","nonInferiorityType":"SUPERIORITY","pValue":"0.4143","pValueComment":"Each comparison was tested using a Bonferroni corrected significance level of 0.017 (0.05/3).","statisticalMethod":"Regression, Linear","paramType":"Median Difference (Final Values)","paramValue":"-0.64","ciPctValue":"98.3","ciNumSides":"TWO_SIDED","ciLowerLimit":"-2.52","ciUpperLimit":"1.24"},{"groupIds":["OG000","OG002"],"groupDescription":"Another major secondary objective was to determine if the change in absolute headache days from baseline to week 24 differed between treatment groups. This objective was assessed using linear regression models, with three pairwise comparisons between treatment groups (Amitriptyline vs. Placebo, Topiramate vs. Placebo, and Amitriptyline vs. Topiramate). The models, and corresponding odds ratios, were adjusted for the two stratification variables (age and baseline number of headache days).","nonInferiorityType":"SUPERIORITY","pValue":"0.9038","pValueComment":"Each comparison was tested using a Bonferroni corrected significance level of 0.017 (0.05/3).","statisticalMethod":"Regression, Linear","paramType":"Median Difference (Final Values)","paramValue":"-0.08","ciPctValue":"98.3","ciNumSides":"TWO_SIDED","ciLowerLimit":"-1.68","ciUpperLimit":"1.52"}]},{"type":"SECONDARY","title":"Tolerability, as Indicated by the Number (Percentage) of Participants That Completed the 24-week Treatment Phase","description":"To assess tolerability, the percentage of subjects who complete the entire 24-week treatment period will be estimated in each of the three groups.","populationDescription":"Tolerability was assessed for all participants included in the primary analysis. Of those randomized, 33 were not included in the primary analysis due to early trial closure.","reportingStatus":"POSTED","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","timeFrame":"24 weeks","groups":[{"id":"OG000","title":"Topiramate","description":"Topiramate enclosed in capsules to maintain the blind was administered orally in a divided dose of 1 capsule twice daily. A target dose was 2 mg per kilogram per day. Dose escalation occurred every two weeks over a period of 8 weeks, with dose modification based on side effects. A 16 week constant-dose (maintenance) phase followed at the highest dosage achieved."},{"id":"OG001","title":"Placebo","description":"Placebo enclosed in capsules to maintain the blind was administered orally twice daily during an 8 week titration period followed by a 16 week maintenance phase (mirroring the other two treatment arms)."},{"id":"OG002","title":"Amitriptyline","description":"Amitriptyline enclosed in capsules to maintain the blind was administered orally in dose of 1 capsule twice daily (AM capsule did not contain medication. A target dose was 1 mg per kilogram per day. Dose escalation occurred every two weeks over a period of 8 weeks, with dose modification based on side effects. A 16 week constant-dose (maintenance) phase followed at the highest dosage achieved."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"130"},{"groupId":"OG001","value":"66"},{"groupId":"OG002","value":"132"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"102"},{"groupId":"OG001","value":"59"},{"groupId":"OG002","value":"106"}]}]}],"analyses":[{"groupIds":["OG001","OG002"],"groupDescription":"Tolerability was assessed by calculating the percent of subjects who completed the entire 24 week treatment period and the corresponding 95% confidence intervals for each treatment group. Concerns regarding tolerability would be raised if the upper bound of a confidence interval was less than 65% or if the percent of subjects who completed the entire 24 week treatment period in either of the active treatment groups was significantly less than the placebo group.","nonInferiorityType":"SUPERIORITY","pValue":"0.1557","statisticalMethod":"Fisher Exact","paramType":"Odds Ratio (OR)","paramValue":"2.07","ciPctValue":"95","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.85","ciUpperLimit":"5.05"},{"groupIds":["OG000","OG001"],"groupDescription":"Tolerability was assessed by calculating the percent of subjects who completed the entire 24 week treatment period and the corresponding 95% confidence intervals for each treatment group. Concerns regarding tolerability would be raised if the upper bound of a confidence interval was less than 65% or if the percent of subjects who completed the entire 24 week treatment period in either of the active treatment groups was significantly less than the placebo group.","nonInferiorityType":"SUPERIORITY","pValue":"0.0754","statisticalMethod":"Fisher Exact","paramType":"Odds Ratio (OR)","paramValue":"2.31","ciPctValue":"95","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.95","ciUpperLimit":"5.62"},{"groupIds":["OG000","OG002"],"groupDescription":"Tolerability was assessed by calculating the percent of subjects who completed the entire 24 week treatment period and the corresponding 95% confidence intervals for each treatment group. Concerns regarding tolerability would be raised if the upper bound of a confidence interval was less than 65% or if the percent of subjects who completed the entire 24 week treatment period in either of the active treatment groups was significantly less than the placebo group.","nonInferiorityType":"SUPERIORITY","pValue":"0.7611","statisticalMethod":"Fisher Exact","paramType":"Odds Ratio (OR)","paramValue":"0.89","ciPctValue":"95","ciNumSides":"TWO_SIDED","ciLowerLimit":"0.49","ciUpperLimit":"1.62"}]},{"type":"SECONDARY","title":"Occurrence of Treatment Emergent Serious Adverse Events","description":"To determine if amitriptyline or topiramate differ from placebo on the occurrence of treatment emergent serious adverse events.","reportingStatus":"POSTED","paramType":"NUMBER","unitOfMeasure":"serious adverse events","timeFrame":"24 weeks of the trial","groups":[{"id":"OG000","title":"Topiramate","description":"Topiramate enclosed in capsules to maintain the blind was administered orally in a divided dose of 1 capsule twice daily. A target dose was 2 mg per kilogram per day. Dose escalation occurred every two weeks over a period of 8 weeks, with dose modification based on side effects. A 16 week constant-dose (maintenance) phase followed at the highest dosage achieved."},{"id":"OG001","title":"Placebo","description":"Placebo enclosed in capsules to maintain the blind was administered orally twice daily during an 8 week titration period followed by a 16 week maintenance phase (mirroring the other two treatment arms)."},{"id":"OG002","title":"Amitriptyline","description":"Amitriptyline enclosed in capsules to maintain the blind was administered orally in dose of 1 capsule twice daily (AM capsule did not contain medication. A target dose was 1 mg per kilogram per day. Dose escalation occurred every two weeks over a period of 8 weeks, with dose modification based on side effects. A 16 week constant-dose (maintenance) phase followed at the highest dosage achieved."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"145"},{"groupId":"OG001","value":"72"},{"groupId":"OG002","value":"144"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"4"},{"groupId":"OG001","value":"2"},{"groupId":"OG002","value":"6"}]}]}],"analyses":[{"groupIds":["OG001","OG002"],"groupDescription":"The occurrence of treatment-related SAE's was assessed in two ways: 1) percentage of subjects who experience any treatment-related SAE in each of the three groups was compared using Fishers exact test; 2) rates of treatment-emergent SAS's across the three groups were compared using a Poisson regression model. However, due to the small number of SAEs that were deemed treatment-emergent (4 in AMI, 1 in TPM, 0 in PBO), the parameter estimates did not converge for the Poisson regression model.","nonInferiorityType":"SUPERIORITY","pValue":"0.3038","statisticalMethod":"Fisher Exact"},{"groupIds":["OG000","OG001"],"groupDescription":"The occurrence of treatment-related SAE's was assessed in two ways: 1) percentage of subjects who experience any treatment-related SAE in each of the three groups was compared using Fishers exact test; 2) rates of treatment-emergent SAS's across the three groups were compared using a Poisson regression model. However, due to the small number of SAEs that were deemed treatment-emergent (4 in AMI, 1 in TPM, 0 in PBO), the parameter estimates did not converge for the Poisson regression model.","nonInferiorityType":"SUPERIORITY","pValue":"1.000","statisticalMethod":"Fisher Exact"},{"groupIds":["OG000","OG002"],"groupDescription":"The occurrence of treatment-related SAE's was assessed in two ways: 1) percentage of subjects who experience any treatment-related SAE in each of the three groups was compared using Fishers exact test; 2) rates of treatment-emergent SAS's across the three groups were compared using a Poisson regression model. However, due to the small number of SAEs that were deemed treatment-emergent (4 in AMI, 1 in TPM, 0 in PBO), the parameter estimates did not converge for the Poisson regression model.","nonInferiorityType":"SUPERIORITY","pValue":"0.2139","statisticalMethod":"Fisher Exact"}]}]},"adverseEventsModule":{"frequencyThreshold":"5","timeFrame":"Adverse events were collected after the ingestion of at least one dose of study drug through study completion, an average of 24 weeks.","eventGroups":[{"id":"EG000","title":"Topiramate","description":"Topiramate enclosed in capsules to maintain the blind was administered orally in a divided dose of 1 capsule twice daily. A target dose was 2 mg per kilogram per day. Dose escalation occurred every two weeks over a period of 8 weeks, with dose modification based on side effects. A 16 week constant-dose (maintenance) phase followed at the highest dosage achieved.","seriousNumAffected":4,"seriousNumAtRisk":145,"otherNumAffected":111,"otherNumAtRisk":145},{"id":"EG001","title":"Placebo","description":"Placebo enclosed in capsules to maintain the blind was administered orally twice daily during an 8 week titration period followed by a 16 week maintenance phase (mirroring the other two treatment arms).","seriousNumAffected":2,"seriousNumAtRisk":72,"otherNumAffected":51,"otherNumAtRisk":72},{"id":"EG002","title":"Amitriptyline","description":"Amitriptyline enclosed in capsules to maintain the blind was administered orally in dose of 1 capsule twice daily (AM capsule did not contain medication. A target dose was 1 mg per kilogram per day. Dose escalation occurred every two weeks over a period of 8 weeks, with dose modification based on side effects. A 16 week constant-dose (maintenance) phase followed at the highest dosage achieved.","seriousNumAffected":6,"seriousNumAtRisk":144,"otherNumAffected":106,"otherNumAtRisk":144}],"seriousEvents":[{"term":"Intussusception","organSystem":"Gastrointestinal disorders","sourceVocabulary":"MedDRA 15.1","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":1,"numAffected":1,"numAtRisk":145},{"groupId":"EG001","numEvents":0,"numAffected":0,"numAtRisk":72},{"groupId":"EG002","numEvents":0,"numAffected":0,"numAtRisk":144}]},{"term":"Contusion","organSystem":"Injury, poisoning and procedural complications","sourceVocabulary":"MedDRA 15.1","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":1,"numAffected":1,"numAtRisk":145},{"groupId":"EG001","numEvents":0,"numAffected":0,"numAtRisk":72},{"groupId":"EG002","numEvents":0,"numAffected":0,"numAtRisk":144}]},{"term":"Traumatic Liver Injury","organSystem":"Injury, poisoning and procedural complications","sourceVocabulary":"MedDRA 15.1","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":1,"numAffected":1,"numAtRisk":145},{"groupId":"EG001","numEvents":0,"numAffected":0,"numAtRisk":72},{"groupId":"EG002","numEvents":0,"numAffected":0,"numAtRisk":144}]},{"term":"Suicide attempt","organSystem":"Psychiatric disorders","sourceVocabulary":"MedDRA 15.1","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":1,"numAffected":1,"numAtRisk":145},{"groupId":"EG001","numEvents":0,"numAffected":0,"numAtRisk":72},{"groupId":"EG002","numEvents":0,"numAffected":0,"numAtRisk":144}]},{"term":"Appendicitis","organSystem":"Infections and infestations","sourceVocabulary":"MedDRA 15.1","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":0,"numAffected":0,"numAtRisk":145},{"groupId":"EG001","numEvents":1,"numAffected":1,"numAtRisk":72},{"groupId":"EG002","numEvents":0,"numAffected":0,"numAtRisk":144}]},{"term":"Pharyngitis streptococcal","organSystem":"Infections and infestations","sourceVocabulary":"MedDRA 15.1","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":0,"numAffected":0,"numAtRisk":145},{"groupId":"EG001","numEvents":1,"numAffected":1,"numAtRisk":72},{"groupId":"EG002","numEvents":0,"numAffected":0,"numAtRisk":144}]},{"term":"Anaphylactic reaction","organSystem":"Immune system disorders","sourceVocabulary":"MedDRA 15.1","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":0,"numAffected":0,"numAtRisk":145},{"groupId":"EG001","numEvents":0,"numAffected":0,"numAtRisk":72},{"groupId":"EG002","numEvents":1,"numAffected":1,"numAtRisk":144}]},{"term":"Syncope","organSystem":"Nervous system disorders","sourceVocabulary":"MedDRA 15.1","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":0,"numAffected":0,"numAtRisk":145},{"groupId":"EG001","numEvents":0,"numAffected":0,"numAtRisk":72},{"groupId":"EG002","numEvents":1,"numAffected":1,"numAtRisk":144}]},{"term":"Mood altered","organSystem":"Psychiatric disorders","sourceVocabulary":"MedDRA 15.1","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":0,"numAffected":0,"numAtRisk":145},{"groupId":"EG001","numEvents":0,"numAffected":0,"numAtRisk":72},{"groupId":"EG002","numEvents":3,"numAffected":3,"numAtRisk":144}]},{"term":"Bronchospasm","organSystem":"Respiratory, thoracic and mediastinal disorders","sourceVocabulary":"MedDRA 15.1","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":0,"numAffected":0,"numAtRisk":145},{"groupId":"EG001","numEvents":0,"numAffected":0,"numAtRisk":72},{"groupId":"EG002","numEvents":1,"numAffected":1,"numAtRisk":144}]}],"otherEvents":[{"term":"Asphasia","organSystem":"Nervous system disorders","sourceVocabulary":"MedDRA 15.1","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":25,"numAffected":23,"numAtRisk":145},{"groupId":"EG001","numEvents":9,"numAffected":7,"numAtRisk":72},{"groupId":"EG002","numEvents":16,"numAffected":13,"numAtRisk":144}]},{"term":"Cognitive Disorder","organSystem":"Nervous system disorders","sourceVocabulary":"MedDRA 15.1","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":25,"numAffected":23,"numAtRisk":145},{"groupId":"EG001","numEvents":8,"numAffected":8,"numAtRisk":72},{"groupId":"EG002","numEvents":18,"numAffected":14,"numAtRisk":144}]},{"term":"Dizziness","organSystem":"Nervous system disorders","sourceVocabulary":"MedDRA 15.1","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":9,"numAffected":9,"numAtRisk":145},{"groupId":"EG001","numEvents":2,"numAffected":1,"numAtRisk":72},{"groupId":"EG002","numEvents":3,"numAffected":3,"numAtRisk":144}]},{"term":"Memory Impairment","organSystem":"Nervous system disorders","sourceVocabulary":"MedDRA 15.1","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":29,"numAffected":24,"numAtRisk":145},{"groupId":"EG001","numEvents":8,"numAffected":7,"numAtRisk":72},{"groupId":"EG002","numEvents":11,"numAffected":11,"numAtRisk":144}]},{"term":"Paresthesia","organSystem":"Nervous system disorders","sourceVocabulary":"MedDRA 15.1","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":67,"numAffected":45,"numAtRisk":145},{"groupId":"EG001","numEvents":6,"numAffected":6,"numAtRisk":72},{"groupId":"EG002","numEvents":10,"numAffected":10,"numAtRisk":144}]},{"term":"Fatigue","organSystem":"General disorders","sourceVocabulary":"MedDRA 15.1","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":40,"numAffected":36,"numAtRisk":145},{"groupId":"EG001","numEvents":12,"numAffected":10,"numAtRisk":72},{"groupId":"EG002","numEvents":48,"numAffected":43,"numAtRisk":144}]},{"term":"Dry Mouth","organSystem":"Gastrointestinal 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