Medical Therapies for Chronic Post-Traumatic Headaches

• ClinicalTrials.gov Identifier: NCT00862095
• Recruitment Status: Terminated
• First Posted: March 16, 2009
• Last Update Posted: April 23, 2013
• Sponsor: Madigan Army Medical Center
• Collaborator: U.S. Army Medical Research and Development Command
• Information provided by (Responsible Party): Jay C. Erickson, Madigan Army Medical Center

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Headache	Drug: Placebo; Drug: Propranolol; Drug: Amitriptyline; Drug: Topiramate	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized Controlled Trial of Medical Therapies for Chronic Post-Traumatic Headaches
• Study Start Date: June 2008
• Actual Primary Completion Date: April 2013
• Actual Study Completion Date: April 2013

Arms and Interventions

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 Name: Inderal
Experimental: Topiramate; Topiramate (target dose 100 mg a day)	Drug: Topiramate; Target dose 100 mg a day for 3 months; Other Name: Topamax
Experimental: Amitriptyline; Amitriptyline (target dose 50 mg a day)	Drug: Amitriptyline; Target does of 50 mg per day for 3 months; Other Name: Elavil

Outcome Measures

Primary Outcome Measures :

1. Headache days per month on the third month of treatment [ Time Frame: Monthly for 4 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Washington

Madigan Army Medical Center

Tacoma, Washington, United States, 98431

Sponsors and Collaborators

Madigan Army Medical Center

U.S. Army Medical Research and Development Command

Investigators

• Principal Investigator: Jay Erickson, MD; Madigan Army Medical Center

More Information

• Responsible Party: Jay C. Erickson, Chief, Neurology Service, Madigan Army Medical Center
• ClinicalTrials.gov Identifier: NCT00862095
• Other Study ID Numbers: 208075
• First Posted: March 16, 2009
• Last Update Posted: April 23, 2013
• Last Verified: April 2013

Additional relevant MeSH terms:

Post-Traumatic Headache; Headache; Pain; Neurologic Manifestations; Signs and Symptoms; Headache Disorders, Secondary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Topiramate; Propranolol; Amitriptyline; Amitriptyline, perphenazine drug combination; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Anticonvulsants; Hypoglycemic Agents; Antidepressive Agents, Tricyclic; Antidepressive Agents; Psychotropic Drugs; Analgesics, Non-Narcotic; Analgesics