Amitriptyline to Prevent Headache After Traumatic Brain Injury
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
| Brain Injuries Post-Traumatic Headache | Drug: Amitriptyline | Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
| Official Title: | Amitriptyline to Prevent Headache After Traumatic Brain Injury |
- Frequency and severity of headaches [ Time Frame: 90 days ]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.
- 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.
| Enrollment: | 50 |
| Study Start Date: | April 2013 |
| Study Completion Date: | February 2016 |
| Primary Completion Date: | February 2016 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: 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.
|
Drug: Amitriptyline
Participants 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).
Other Name: Elavil
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Experimental: 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.
|
Drug: Amitriptyline
Participants 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).
Other Name: Elavil
|
Show Detailed Description
Eligibility
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 60 Years (Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01856270
| United States, Washington | |
| Harborview Medical Center | |
| Seattle, Washington, United States, 98109 | |
| Principal Investigator: | Jeanne M Hoffman, PhD | University of Washington |
More Information
Additional Information:
| Responsible Party: | Jeanne Hoffman, Professor, University of Washington |
| ClinicalTrials.gov Identifier: | NCT01856270 History of Changes |
| Other Study ID Numbers: |
44274-B |
| First Submitted: | May 10, 2013 |
| First Posted: | May 17, 2013 |
| Last Update Posted: | October 12, 2017 |
| Last Verified: | May 2016 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
Keywords provided by Jeanne Hoffman, University of Washington:
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Traumatic brain injury Post-traumatic headache Drug therapy |
Additional relevant MeSH terms:
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Wounds and Injuries Brain Injuries Headache Post-Traumatic Headache Brain Diseases Central Nervous System Diseases Nervous System Diseases Craniocerebral Trauma Trauma, Nervous System Pain Neurologic Manifestations Signs and Symptoms Headache Disorders, Secondary Headache Disorders Amitriptyline |
Amitriptyline, perphenazine drug combination Antidepressive Agents, Tricyclic Antidepressive Agents Psychotropic Drugs Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs Adrenergic Uptake Inhibitors Neurotransmitter Uptake Inhibitors Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action Adrenergic Agents Neurotransmitter Agents |