Amitriptyline to Prevent Headache After Traumatic Brain Injury
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Frequency of Headaches
研究概览
简要总结
The investigators propose to conduct a 2-arm, open-label pilot study to determine if early treatment with amitriptyline will decrease the frequency and severity of headaches after mild traumatic brain injury (TBI). Amitriptyline is a tricyclic antidepressant that is commonly available and inexpensive. It is used as a first-line drug for primary headache prevention in a very low dose range of 10-50 mg.
- Specific Aim 1 is to conduct a 2-arm open-label study to examine the effect of preventive treatment with amitriptyline on the frequency and severity of headache after mild TBI.
- Specific Aim 2 is to collect data needed for design of a Phase 3 study, including an estimate of effect size, headache variability, and desirable drug treatment start date.
- Specific Aim 3 is to examine the feasibility of using headache diaries with individuals with mild TBI.
- Specific Aim 4 is to establish the safety and tolerability of amitriptyline for the prevention of headache after mild TBI.
The investigators hypothesize that early preventive treatment with amitriptyline will avert the development of chronic post-traumatic headache (PTH) as compared to rates of headache from a recent natural history study on PTH after mild TBI.
The investigators propose to enroll inpatient subjects from a Level I trauma center as well as from outpatient clinics and from the general community with a diagnosis of mild TBI. Subjects will be screened for current headache. After baseline assessment, 72 subjects with current headache will be randomized to one of 2 groups. Group 1 will immediately begin amitriptyline and or Group 2 will be followed and begin amitriptyline at Day 30. All subjects will be asked to complete a daily headache diary beginning on Day 1 of the study. A detailed medical history and headache survey will be completed. Subjects will have a scheduled stepped increase in the drug dosage every week for 3 weeks to the maximum study dosage of 50 mg. Weekly telephone calls will monitor for adverse events and compliance with the drug and headache diary. Clinic visits will occur at 30, 60 and 90 days. The 30 day clinic visit will include cognitive testing to assess for differences between groups and initiation of drug treatment for Group 2. Both 30 and 60 day visits will include review of headache diary, potential adverse effects, and pill counts. The 90 day visit will be for outcome assessment. In addition, the headache survey will be repeated by telephone at Day 180.
详细描述
Research Hypothesis and Aims: The ultimate aim of this research is to determine whether early treatment using amitriptyline can prevent the development of chronic headache after TBI. This proposal is for preliminary work that will give some indication of the effect of amitriptyline and provide information needed to design a definitive study of the efficacy of amitriptyline for the prevention of chronic post-traumatic headache.
Specific Aim 1 is to conduct a two-arm open-label study to examine the effect of preventive treatment with amitriptyline on the frequency and severity of headache after mild TBI compared to that seen in our observational study on the natural history of headache after mild TBI.
Specific Aim 2 is to collect data needed for design of a Phase III study, including an estimate of effect size, the variability in the number of headache days in those with mild TBI, and determining a desirable initiation date for preventive treatment (e.g., week 1 or month 1 after injury).
Specific Aim 3 is to examine the feasibility of headache diary use in individuals with mild TBI.
Specific Aim 4 is to establish the safety and tolerability of amitriptyline for the prevention of headache after mild TBI.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Acute mild TBI (Glasgow Coma Scale of 13-15 on emergency department evaluation, any period of loss of consciousness (LOC) < than 30 minutes, alteration of consciousness or post-traumatic amnesia (not to exceed 24 hours)
- •Ability to give consent
- •Ages 18-60
- •Access to a telephone
- •Current headache (new headache or headache worse than prior to injury)
排除标准
- •Does not speak English
- •Diagnosed seizure disorder
- •Myocardial infarction in prior 6 months
- •Cardiac arrhythmia requiring medication treatment
- •Prolonged Q-T interval on electrocardiogram
- •Psychosis
- •Intoxication on hospital admission sufficient enough to cloud the diagnosis of mild TBI
- •Incarceration or homelessness
- •Allergy to amitriptyline
- •Current treatment with amitriptyline or other tricyclic antidepressant
- •Currently taking any medication not recommended for use with amitriptyline due to the potential for Q-T interval prolongation. Examples of this include: Class I, I-A or II antiarrhythmics, TCA's, MAOI's, selected fluoroquinolones (gatifloxacin, moxifloxacin), selected antipsychotic medications (haloperidol, risperidone, quetiapine), selected antiretroviral medications, cisapride, chloroquine, chlorpromazine, prochlorperazine, promethazine, citalopram, fluoxetine, erythromycin, methadone
- •History of glaucoma
- •History of prostate disease or current urinary retention
研究组 & 干预措施
Amitriptyline Immediate
The Amitriptyline Immediate group will begin study drug immediately after enrollment. Immediate Drug participants will be started on one 10 mg capsule each evening. The dosage will be adjusted upwards to 25 mg daily for Week 2 to a maximum of 50 mg daily by Week 3.
干预措施: Amitriptyline (Drug)
Amitriptyline Delayed
The Amitriptyline Delayed group will start the study drug at the Day 30 visit on one 10 mg capsule each evening. The dosage will be adjusted upwards to 25 mg daily for Week 2 to a maximum of 50 mg daily by Week 3.
干预措施: Amitriptyline (Drug)
结局指标
主要结局
Frequency of Headaches
时间窗: 90 days
Number of subjects reporting an average of at least one headache per week
Severity of Headache
时间窗: 90 days
Number of subjects with headache reporting an average pain of at least 6 on a 0-10 scale with 0=no pain and 10=worst pain.
次要结局
- Number of Participants With Adverse Events Possibly Related to Study Medication(Day 1 through Day 90)
- Rey Auditory Verbal Learning Test (Total)(30 days)
- Wechsler Adult Intelligence Scale (WAIS) IV Digit Symbol(30 days)
- Rey Auditory Verbal Learning Test (Long)(30 days)
- Trail Making Test (A)(30 days)
- Trail Making Test (B)(30 days)
- Rey Auditory Verbal Learning Test (Short)(30 days)
研究者
Jeanne Hoffman
Professor
University of Washington