Amitriptyline and Topiramate in the Prevention of Childhood Migraine
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 488
- 试验地点
- 35
- 主要终点
- Number (Percentage) of Participants Reporting a ≥ 50% Reduction in Headache Days
研究概览
简要总结
The purpose of this research study is to test two medicines for migraine prevention in children and adolescents.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 8 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 ≥
- •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
- •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.
排除标准
- •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.
研究组 & 干预措施
Amitriptyline
Drug to be administered twice daily.
干预措施: Amitriptyline (Drug)
Topiramate
Drug to be administered twice daily.
干预措施: Topiramate (Drug)
Placebo
To be administered twice daily.
干预措施: Placebo (Drug)
结局指标
主要结局
Number (Percentage) of Participants Reporting a ≥ 50% Reduction in Headache Days
时间窗: 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.
次要结局
- Change in Absolute Headache Disability Score on PedMIDAS(baseline and 24 week endpoint)
- Change in Number of Headache Days(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(24 weeks)
- Occurrence of Treatment Emergent Serious Adverse Events(24 weeks of the trial)