Clinical Trial: Amitriptyline to Prevent Headache After Traumatic Brain Injury

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Amitriptyline to Prevent Headache After Traumatic Brain Injury

Brief Summary:

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

Detailed Summary:

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.

Hypothesis: Preventive treatment of early headaches with amitriptyline after mild TBI results in decreased prevalence of recurrent headache (percent of participants having at least 1 headache/week) and severe headaches (percent of participants having headaches with an average pain of 5 or higher) at three months as compared to the frequency and severity of headache in those followed in the natural history study who received usual care.

Headache frequency and severity are the most frequently used measures of medication efficacy in headache research. We will measure the number of headaches per week and severity ratings (1-10)using headache diaries and report to research staff.



Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Headache Impact Test - 6 [ Time Frame: Day 90, Day 180 ]
    The HIT-6 is a well-developed brief measure of the effect headaches are having on patients, that is, a headache disability scale.72, 73 This 6 item test has excellent reliability and validity, including construct validity.
  • Rivermead Post-Concussion Symptoms Questionnaire (RPQ) [ Time Frame: 90 days ]
    The RPQ is a widely used measure that details the occurrence and severity of 16 common physical and cognitive symptoms after TBI.
  • Short Form-12® Health Survey (SF-12) [ Time Frame: 90 days ]
    The SF-12 was originally developed in 1994 as a shorter alternative to the SF-36. The SF-36 is a well validated, widely used general health related quality of life measure.
  • Number of participants with adverse events [ Time Frame: Day 1 through Day 90 ]
    The number and types of adverse events will be monitored on a weekly basis and will be divided into likelihood of association with the drug and into severity classes.
  • Headache characteristic survey [ Time Frame: Day 1, Day 30, Day 60, Day 90, Day 180 ]
    This survey will gather information on several factors that will be used to comprehensively describe PTH and its treatment including International Classification of Headache Disorders, 2nd edition (ICHD) criteria (type of headache by characteristics such as location, duration, severity, associated symptoms.
  • Insomnia Severity Index [ Time Frame: 90 days ]
    This is a brief self-report of the person's subjective evaluation of insomnia. It targets the subject symptoms of insomnia as well as the concern or impact of the symptoms. This includes sleep onset and maintenance, satisfaction with current sleep pattern, interference with daily functioning, impairment and distress or concern.
  • Patient Health Questionnaire-9 (PHQ-9 [ Time Frame: 90 days ]
    The PHQ-9 will be used to assess depression. We are including this to measure any antidepressant effect of amitriptyline which was first used for this purpose. The nine items on the measure correspond with Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria for depression, with each item scored from "not at all" to "nearly every day".
  • Rey Auditory Verbal Learning Test [ Time Frame: 30 days ]
    The Rey Auditory Verbal Learning Test will be administered at 30 days to detect potential changes in cognitive function due to study drug.
  • Trail Making Test [ Time Frame: 30 days ]
    Trail Making Test will be given at 30 days to detect any impact of study drug on cognition.
  • Wechsler Adult Intelligence Scale (WAIS) IV Digit Symbol [ Time Frame: 30 days ]
    The WAIS IV Digit Symbol test will be given to detect any effect of study drug on cognition.


Original Secondary Outcome: Same as current

Information By: University of Washington

Dates:
Date Received: May 10, 2013
Date Started: April 2013
Date Completion:
Last Updated: May 20, 2016
Last Verified: May 2016