Brain Injuries | Amitriptyline to Prevent Headache After Traumatic Brain Injury
Brain Injuries research study
What is the primary objective of this study?
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.
Who is eligible to participate?
Inclusion Criteria: - 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) Exclusion Criteria: - 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
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Drug:AmitriptylineParticipants with headache will be enrolled within the first 12 weeks after injury and will be randomly assigned to 2 groups (see Table 1 for summary of protocol). Group 1 will be assessed within 3 months of injury (baseline, Day 0) (when they will receive their initial ramp-up dosage containers; see Table 2 for dosing), Day 30 and Day 60 (to monitor compliance and distribute study drug), and for final outcome on Day 90. Group 2 will be assessed within 3 months of injury (baseline, Day 0) but will not receive medication until their Day 30 visit. Those in group 2 who report headache at Day 30 will receive their initial dosage container and will then be reassessed at Day 60 (to monitor compliance and distribute study drug) and Day 90 (final outcome).
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
Amitriptyline ImmediateThe 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.
Amitriptyline DelayedThe 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.
Start Date: April 2013
Completed Date: February 2016
Phase: Phase 2
Primary Outcome: Frequency of Headaches
Secondary Outcome: Number of Participants With Adverse Events Possibly Related to Study Medication
Study sponsors, principal investigator, and references
Principal Investigator: Jeanne M Hoffman, PhD
Lead Sponsor: University of Washington