Amitriptyline to Prevent Headache After Traumatic Brain Injury

NCT01856270 | Completed Phase 2 Results DMC

• 1 other identifier: STUDY00001333
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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. 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.

Conditions

Brain Injuries; Post-Traumatic Headache

Keywords

Traumatic brain injury; Post-traumatic headache; Drug therapy

Outcome Measures

Primary Outcomes (2)

• Frequency of Headaches

  Number of subjects reporting an average of at least one headache per week

  90 days

• Severity of Headache

  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.

  90 days

Secondary Outcomes (7)

• Number of Participants With Adverse Events Possibly Related to Study Medication

  Day 1 through Day 90

• Rey Auditory Verbal Learning Test (Total)

  30 days

• Rey Auditory Verbal Learning Test (Short)

  30 days

• Rey Auditory Verbal Learning Test (Long)

  30 days

• Trail Making Test (A)

  30 days

Study Arms (2)

Amitriptyline Immediate

EXPERIMENTAL

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

Amitriptyline Delayed

EXPERIMENTAL

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

Interventions

Amitriptyline DRUG

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).

Also known as: Elavil

Amitriptyline Delayed; Amitriptyline Immediate

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Washington: lead

Study Sites (1)

Harborview Medical Center

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Brain Injuries; Post-Traumatic Headache; Brain Injuries, Traumatic

Interventions

Amitriptyline

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Headache Disorders, Secondary; Headache Disorders

Intervention Hierarchy (Ancestors)

Dibenzocycloheptenes; Benzocycloheptenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Limitations and Caveats

This was a prevention study recruiting from hospital inpatients or from the ED with a diagnosis of mild TBI. We were unable to recruit an adequate number of subjects and had difficult follow up. Of those recruited, we followed only 54%.

Results Point of Contact

• Title: Dr. Jeanne Hoffman
• Organization: University of Washington

jeanneh@uw.edu

206-221-6511

Study Officials

• Jeanne M Hoffman, PhD

  University of Washington

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 10, 2013
• First Posted: May 17, 2013
• Study Start: April 1, 2013
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: September 19, 2024
• Results First Posted: December 22, 2017

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)