Treximet for Prevention of Post Traumatic Headache Associated With Cognitive Dysfunction
Condition: Post-Traumatic Headache
MeSH terms: Post-Traumatic Headache; Headache; Cognitive Dysfunction
Intervention: sumatriptan/naproxen sodium; Placebo
Intervention description: Each tablet of Treximet for oral administration contains sumatriptan 85mg / naproxen sodium 500mg. Study medication is to be administered 1 tablet per day at the same time each day x 30 days in the Treatment Period.; Each tablet of placebo for oral administration matches Treximet. Placebo is to be administered 1 tablet per day at the same time each day x 30 days in the Treatment Period.
Intervention MeSH terms: Naproxen; Sumatriptan
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Headache; Post-traumatic headache; Brain injury; Cognitive impairment

Summary:

      This study will evaluate the effectiveness of Treximet when taken for post traumatic headache
      by measuring any change in the number of headache days or any change in a subject's ability
      to think following treatment with study medication. Eligible subjects will complete 3 visits.
      Following Visit 1, subjects will treat with their usual medication and document headache
      symptoms and therapy in a Headache Diary. After 30 days, subjects will return for Visit 2 and
      be randomized (like the flip of a coin) to receive Treximet or matching placebo to treat at
      the same time each day. Treximet will be provided to treat any headache that occurs. Subjects
      will complete a daily Diary. After 30 days, subjects will exit the study at Visit 3.
    

Eligibility criteria:

        Inclusion Criteria:

        Subject

          -  is male or female between the ages of 18-65. A female is eligible to enter and
             participate in this study if she is of: a.non-childbearing potential (i.e.,
             physiologically incapable of becoming pregnant); or,b. child-bearing potential, has a
             negative pregnancy test (urine or serum) at Visit 2, 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 to account for
             elimination of the investigational drug; subjects utilizing this method must agree to
             use an alternate method of contraception if they should 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 that the 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); or, Any other barrier methods (only if used in
             combination with any of the above acceptable methods); or, Any other methods with
             published data showing that the highest expected failure rate for that method is less
             than 1% per year.

          -  is formally diagnosed with International Classification of Headache Disorders (ICHD)
             5.2.2 chronic post traumatic headache

          -  has >15 headache days per month in past 3 months

          -  has headache that, if left untreated, would have at least 1 symptom of migraine
             (nausea, vomiting, photophobia, or phonophobia) or respond to a triptan or
             ergotamine-containing medication with at least 50% of headaches

          -  is medically stable as determined by the Investigator

          -  if taking a headache preventive medication, has been on a stabilized dosage for at
             least 30 days prior to screening.

          -  if taking any concomitant medications, is on a stabilized dosage at the discretion of
             the investigator

          -  has chronic headache history only after the traumatic brain injury (TBI)

          -  is able to understand and communicate intelligibly with the study observer

          -  is able to take oral medication, adhere to the medication regimens and perform study
             procedures

          -  is able to read and comprehend written instructions and be willing to complete all
             procedures and assessments required by this protocol

          -  is able to demonstrate the willingness to participate by signing and understanding an
             informed consent after full explanation of the study

          -  has self-reported cognitive inefficiency or "brain-fog" during headache

        Exclusion Criteria:

        Subject

          -  has a history of serotonin syndrome

          -  has any medical condition that, in the opinion of the investigator, could alter the
             response to study medication or confound the results of the study

          -  is female of childbearing potential not using adequate contraceptive measures

          -  has history of retinal, basilar or hemiplegic migraine, cluster headache, or secondary
             headaches (such as due to infection, alterations of homeostasis, ear nose and throat
             (ENT) or psychiatric disorders, cranial or cervical disorders or neuralgias)

          -  in the investigator's opinion, is likely to have unrecognized cardiovascular or
             cerebrovascular disease (based on history or the presence of risk factors including
             but not limited to, hypertension, hypercholesterolemia, smoker, obesity, diabetes, or
             family history of coronary artery disease)

          -  has blood pressure ≥140/90 millimeters of mercury (mmHg) in 2 out of 3 BP measurements
             at screening or is taking any angiotensin-converting enzyme (ACE) inhibitor or
             angiotensin receptor blocker

          -  has a history of significant congenital heart disease, cardiac arrhythmias requiring
             medication, or a history of a clinically significant electrocardiogram abnormality
             that, in the investigator's opinion, contraindicates participation in this study

          -  has evidence or history of any ischemic vascular diseases including: ischemic heart
             disease, ischemic abdominal syndromes, peripheral vascular disease or Raynaud's
             Syndrome, or signs/symptoms consistent with any of the above

          -  has evidence or history of central nervous system pathology including stroke and/or
             transient ischemic attacks (TIAs), epilepsy or structural brain lesions which lower
             the convulsive threshold; or has been treated with an antiepileptic drug for seizure
             control within 5 years prior to screening

          -  has a history of impaired hepatic or renal function that, in the investigator's
             opinion, contraindicates participation in this study

          -  has hypersensitivity, intolerance, or contraindication to the use of any triptan,
             nonsteroidal antiinflammatory drug (NSAID) or aspirin (including all sumatriptan and
             naproxen preparations) or has nasal polyps and asthma

          -  is currently taking, or has taken in the previous three months, a migraine
             prophylactic medication containing methysergide; or is taking a migraine or menstrual
             migraine prophylactic medication that is not stabilized (i.e. start or change of dose
             within 30 days prior to screening)

          -  has a recent history of regular use of opioids or barbiturates for treatment of their
             migraine headache and/or other non-migraine pain or any medication overuse that in the
             opinion of the investigator has exacerbated or contributed to the current headache
             pattern of the subject.

          -  has taken, or plans to take, a monoamine oxidase inhibitor (MAOI), including herbal
             preparations containing St. John's Wort (Hypericum perforatum), anytime within the 2
             weeks prior to screening through 2 weeks post final study treatment.

          -  has history of any bleeding disorder or is currently taking any anti-coagulant or any
             antiplatelet agent.

          -  has evidence or history of any gastrointestinal surgery or GI ulceration or
             perforation in the past six months, gastrointestinal bleeding in the past year; or
             evidence or history of inflammatory bowel disease

          -  is pregnant, actively trying to become pregnant, or breast feeding

          -  has evidence of alcohol or substance abuse within the last year or any concurrent
             medical or psychiatric condition which, in the investigator's judgment, will likely
             interfere with the study conduct, subject cooperation, or evaluation and
             interpretation of the study results, or which otherwise contraindicates participation
             in this clinical trial.

          -  has participated in an investigational drug trial within the previous four weeks or
             plans to participate in another study at any time during this study.