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