Naratriptan for the Treatment of Post Traumatic Headache Associated With Cognitive Dysfunction

Study Overview
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Brief Summary
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The purpose of this study is to determine whether naratriptan, a medication approved for treatment of migraine, is effective in the treatment of post traumatic headache associated with cognitive dysfunction.

Detailed Description
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Naratriptan has demonstrated efficacy in relieving headache. Other studies have demonstrated that primary headaches with at least one headache feature are likely to respond to triptans. In addition, there are anecdotal reports of triptans being effective in post traumatic headaches, especially if headache features are noted in the patient's history. Further, there are several small pilot studies with triptans demonstrating a prompt improvement in headache-induced cognitive changes. Cognitive performance can be measured by the Mental Efficiency Workload Test (MEWT), a handheld Palm neuropsychological test battery that measures mental efficiency. This tool can be used to demonstrate short and long term improvement in mental status beyond that seen at baseline. Informal observations by the protocol authors have suggested that the use of triptans on a routine basis may ameliorate the headache and associated symptomatology of post traumatic headache. Therefore, this study is undertaken to study the use of naratriptan in the treatment of post traumatic headache. Roger K. Cady, MD, serves as the sponsor. The study is funded by GlaxoSmithKline. 56 subjects with a formal diagnosis of Chronic post-traumatic headache attributed to mild head injury (IHS/ICHD-II 5.2.2) and with self-reported mild cognitive inefficiency secondary to headache will be enrolled. Subjects meeting inclusion criteria will complete a physical examination and baseline testing and be randomized 1:1 to naratriptan 2.5mg bid x 30 days or a matched placebo bid x 30 days. A daily diary will document response to treatment. Subjects will return to the clinic at Day 10 and Day 30 and complete phone contacts at Days 5, 15, 21, 32 and 90. Information will be collected throughout the study on questionnaires related to headache impact, general health, satisfaction with medication, and quality of life. Cognition will be measured using the MEWT.

Official Title
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Evaluation of the Efficacy of Naratriptan for the Treatment and Prevention of Post Traumatic Headache Associated With Cognitive Dysfunction

Conditions
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Post Traumatic Headache

Intervention / Treatment
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* Drug: naratriptan HCl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females between the ages of 18-55. A female is eligible to enter and participate if she is of: non-childbearing potential (i.e., physiologically incapable of becoming pregnant); or, child-bearing potential, has a negative pregnancy test (urine or serum) at screen, and agrees to one of the following: Complete abstinence from intercourse from 2 weeks prior to administration of the investigational product, throughout the study, and for a time interval (5 days) after completion or premature discontinuation from the study; subjects utilizing this method must agree to use alternate method of contraception if they become sexually active and will be queried on whether they have been abstinent when they present to the clinic for the Final Visit or, Female sterilization; or, Sterilization of male partner; or, Implants of levonorgestrel; or, Injectable progestogen; or, Oral contraceptive (combined or progestogen only); or, Any intrauterine device (IUD) with published data showing highest expected failure rate is less than 1% per year (not all IUDs meet this criterion); or, Spermicide plus a mechanical barrier (e.g., spermicide plus a male condom or a female diaphragm). Any other barrier methods (only if used in combination with any of the above acceptable methods) or, Any other methods with published data showing highest expected failure rate for that method is less than 1% per year. Formally diagnosed ICHD 5.2.2 chronic post traumatic headache Have had traumatic brain injury (TBI) not more than 5 years prior to enrollment Medically stable as determined by Investigator On stabilized dosage of any headache preventive medications for 3 months prior to screening On stabilized dosage of concomitant medications at discretion of investigator Chronic headache history only after the TBI Able to understand and communicate intelligibly with study observer Able to take oral medication, adhere to the medication regimens and perform study procedures Able to read and comprehend written instructions and be willing to complete all procedures and assessments required by protocol Subject is able to demonstrate willingness to participate by signing and understanding an informed consent after full explanation of study Self-reported cognitive inefficiency or brain-fog during headache Exclusion Criteria: History of hypersensitivity to triptan-like medication Pathology of salivary glands such as sialadenitis (e.g., Sjorgen's Syndrome, viral or bacterial sialadenitis, or obstructive sialadenitis) Any condition or symptom that would knowingly alter content of saliva History of, symptoms or signs of ischemic cardiac, cerebrovascular or peripheral vascular syndromes or other significant underlying cardiovascular disease. Ischemic cardiac syndromes include, but are not limited to, angina pectoris of any type (e.g. stable angina of effort and vasospastic forms of angina such as Prinzmetal variant, all forms of myocardial infarction, and silent myocardial ischemia. Cerebrovascular syndromes include, but are not limited to, strokes of any type as well as transient ischemic attacks. Peripheral vascular disease includes, but is not limited to, ischemic bowel disease. Any medication overuse that in the opinion of the investigator has exacerbated or contributed to current headache pattern of subject Uncontrolled hypertension, severe renal impairment, severe hepatic impairment, hemiplegic or basilar headache History of hypersensitivity to naratriptan or any components Pregnant, trying to get pregnant, or lactating Recent history of abuse of alcohol or other drugs that would interfere with participation Participation in another investigative drug study within previous 30 days Chronic pain syndromes, fibromyalgia, Gulf War Syndrome, and other multisystem diseases characterized by poor or no response to pain-reducing interventions

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br>Naratriptan 2.5 mg tablet bid x 30 days | Drug: naratriptan HCl<br>* naratriptan 2.5mg tablet bid x 30 days OR matching placebo<br>* Other names: Amerge;|
| Placebo Comparator: B<br>placebo matching naratriptan 2.5 mg tablet | Drug: naratriptan HCl<br>* naratriptan 2.5mg tablet bid x 30 days OR matching placebo<br>* Other names: Amerge;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Headache Days | Number of headache days as measured by the Headache Diary | Day 30 | 
| Headache Impact Test-6 (HIT-6) Score | Impact of headache symptoms on subject's life as measured by HIT-6 questionnaire scores. Possible scores range from 36 to 78. Score of 48 or less indicates headache has little impact on life. Score of 60-78 indicative of very severe impact. | Day 0, Day 30 | 
| Mental Efficiency Workload Test (MEWT) Performance Index Score | Cognitive function as measured by Performance Index scores on the Mental Efficiency Workload Test (MEWT). On the performance index scale of 1 to 10, 1 indicates the poorest level and 10 indicates the best level of cognitive functioning. Tests include: Simple reaction time, Running memory, Matching to sample, Math processing and a sleep scale. | Day 0, Day 10, Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Satisfaction With Medication Score | Subject overall satisfaction with effectiveness of the therapy as measured by score on the Satisfaction with Medication questionnaire. Scale range: Very satisfied, Satisfied, Neutral, Dissatisfied, Very dissatisfied. | Day 30, Day 90 | 
| Quality of Life Scores | Quality of life as measured by Migraine Specific Quality of Life questionnaire (MSQ) scores. 14 questions ask how often headaches have interfered with specific daily activities in previous 4 weeks. 6-point scale ranges from None of the time to All of the time. | Day 0, Day 30, Day 90 | 
| Sustained Treatment Effect | Sustained treatment effect as measured by the MEWT Performance Index score compared to change in number of Headache Days. Results would be presented in the form of a correlation analysis. There is an expected negative correlation as performance index increases and number of headache days decrease (a correlation of -1). | Day 0, Day 10, Day 30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Post traumatic headache, Head trauma, Head injury, Headache, Naratriptan