Medical Therapies for Chronic Post-Traumatic Headaches

A Randomized Controlled Trial of Medical Therapies for Chronic Post-Traumatic Headaches

To determine if propranolol, amitriptyline, or topiramate decreases headache frequency in patients with chronic post-traumatic headaches.

Study Overview

• Status: Terminated
• Conditions: Headache
• Intervention / Treatment: Drug: Placebo; Drug: Propranolol; Drug: Topiramate; Drug: Amitriptyline

Detailed Description

A total of 240 patients meeting International Classification of Headache Disorders (ICHD) diagnostic criteria for chronic post-traumatic headaches will be enrolled. Subjects will be recruited from the Neurology Clinic at Madigan Army Medical Center. Study participants will be U.S. Army soldiers who sustained a mild traumatic head injury while deployed to a combat theater resulting in chronic post-traumatic headaches. Subjects will be randomized to placebo, propranolol (target dose 80 mg a day), amitriptyline (target dose 50 mg a day), or topiramate (target dose 100 mg a day) for 3 months.

The primary outcome measure will be the mean number of headache days per month on the third month of treatment. Secondary outcome measures will include the proportion of subjects with at least a 25% reduction in headache frequency, headache severity (0-10 scale), headache duration (hours), headache-related disability (measured by the Headache Impact Test and Migraine Disability Assessment Scale), PTSD symptom checklist score, and medication side effects and tolerability.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Washington
    • Tacoma, Washington, United States, 98431
      • Madigan Army Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Patient meets ICHD criteria for chronic post-traumatic headaches (see below).
2. Patient is 18-50 years old.
3. Patient has experienced 6 or more days of headache per month for each of the last 2 months.
4. Patient has full capacity to provide informed consent.
5. Patient will be available for all study-related visits over the next 4 months.
6. Patient must be eligible to receive care at Madigan Army Medical Center

International Classification of Headache Disorders (version 2) diagnostic criteria for chronic post-traumatic headaches attributed to mild head injury:

1. Headaches beginning within 1 week of mild traumatic head injury.
2. Headaches persisting > 3 months after head trauma.

3. Head trauma with all of the following:

   • no loss of consciousness or loss of consciousness < 30 minutes
   • Glasgow Coma Score (GCS) 13-15
   • symptoms or signs diagnostic of concussion

Exclusion criteria:

1. Patient has another headache disorder not attributable to head trauma which accounts for at least half of the patient's headache episodes.
2. Patient is currently taking propranolol, amitriptyline, or topiramate for any reason.
3. Patient previously tried propranolol, amitriptyline, or topiramate for headache treatment.
4. Patient started a new treatment for headache prevention within the last 6 weeks. Prophylactic treatments initiated prior to 6 weeks ago are allowed as long as the dose or regimen is stable. Medications for aborting acute headaches are also allowed.
5. Patient previously tried more than two medications for headache prevention.
6. Patient is using narcotic analgesics on average more than 10 days a month.
7. Patient has a medical condition or is taking a medication that is considered a contraindication for propranolol, topiramate, or amitriptyline. Medical conditions include liver disease, renal impairment, cardiac dysrhythmias, untreated thyroid disease, orthostatic hypotension, asthma requiring treatment with inhalers, glaucoma, kidney stones, insulin-requiring diabetes, or pregnancy.
8. Patient has known hepatic, renal, or cardiac disorders.
9. Patient drinks on average more than two servings of alcohol (2 oz hard liquor, 5 oz wine, 12 oz beer) per day or more than 3 servings at one time on a weekly basis.
10. Patient has abnormalities on baseline EKG.
11. Patient has major depression defined as a score >15 on the Patient Health Questionnaire-9.
12. Patient is pregnant, planning to become pregnant in the next year, or is a female of reproductive potential who is not using a reliable form of birth control.
13. Patient has cognitive impairment defined as mini-mental status exam score <27.
14. SBP < 90, HR < 50, or HR > 100.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: FACTORIAL
• Masking: TRIPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Placebo group	Drug: Placebo; Every month for 3 months
EXPERIMENTAL: Propranolol; Propranolol (target dose 80 mg a day)	Drug: Propranolol; target does 80 mg per day for 3 months; Other Names: Inderal
EXPERIMENTAL: Topiramate; Topiramate (target dose 100 mg a day)	Drug: Topiramate; Target dose 100 mg a day for 3 months; Other Names: Topamax
EXPERIMENTAL: Amitriptyline; Amitriptyline (target dose 50 mg a day)	Drug: Amitriptyline; Target does of 50 mg per day for 3 months; Other Names: Elavil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Headache days per month on the third month of treatment	Monthly for 4 weeks

Collaborators and Investigators

• Sponsor: Madigan Army Medical Center
• Collaborators: U.S. Army Medical Research and Development Command
• Investigators: Principal Investigator: Jay Erickson, MD, Madigan Army Medical Center

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (ACTUAL): April 1, 2013
• Study Completion (ACTUAL): April 1, 2013

Study Registration Dates

• First Submitted: March 12, 2009
• First Submitted That Met QC Criteria: March 13, 2009
• First Posted (ESTIMATE): March 16, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): April 23, 2013
• Last Update Submitted That Met QC Criteria: April 22, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Headache Disorders; Headache Disorders, Secondary; Headache; Post-Traumatic Headache; Hypoglycemic Agents; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Anticonvulsants; Antidepressive Agents, Tricyclic; Adrenergic Uptake Inhibitors; Propranolol; Amitriptyline; Topiramate
• Other Study ID Numbers: 208075