CGRP, Estrogen, Cortisol, VIP, α-Amylase, PGE2, PGI2 and ß-Endorphin Levels in Menstrual Migraine Before and After Treximet
Condition: Menstrual Migraine
MeSH terms: Migraine Disorders; Premenstrual Syndrome
Intervention: Treximet; Placebo
Intervention description: Tablet for oral administration contains sumatriptan 85mg / naproxen sodium 500mg.; A placebo tablet matching Treximet for oral administration.
Intervention MeSH terms: Naproxen; Sumatriptan
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 41.0
Sex: Female
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: No
Keywords: Menstrual migraine; Menstrually-related migraine; Treximet; CGRP; calcitonin gene-related peptide

Summary:

      The purpose of this study is to (1) evaluate pain-free efficacy of Treximet™ following
      treatment of menstrual migraine, (2) investigate levels of Calcitonin gene-related peptide
      (CGRP), estrogen, cortisol, vasoactive intestinal peptide (VIP), alpha (a)-amylase,
      Prostaglandin E2 (PGE2), Prostaglandin I2 (PGI2) and beta (ß)-endorphin in saliva before and
      after Treximet™, (3) evaluate efficacy of Treximet™ to return to baseline levels following
      treatment, and (4) correlate estrogen in saliva vs. urinary estradiol at mid-luteal, onset of
      menstrually-related migraine, and after successful treatment with Treximet™.
    

Eligibility criteria:

        Inclusion Criteria:

        Subject

          1. is female between the ages of 18-45 and, if of 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,

               -  History of bilateral tubal ligation

               -  Sterilization of male partner; or,

               -  Implants of levonorgestrel; or,

               -  Injectable progestogen; or,

               -  Oral contraceptive (combination therapy with ethinyl estradiol plus a progestin)
                  with a placebo week every 1-3 months; 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.

          2. is formally diagnosed with International Classification of Headache Disorders (ICHD)
             menstrual migraine

          3. has regular and predictable monthly menstrual cycles within a range of 22-32 days for
             the past 3 cycles.

          4. has fewer than 15 headache days per month in past 3 months

          5. 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

          6. has a history of reliably predicting menstrual migraine headache onset at least 70% of
             the time

          7. is medically stable as determined by the Investigator

          8. if taking any concomitant medications, is on a stabilized dosage at the discretion of
             the investigator

          9. is able to understand and communicate intelligibly with the study observer

         10. is able to take oral medication, adhere to the medication regimens and perform study
             procedures

         11. is able to read and comprehend written instructions and be willing to complete all
             procedures and assessments required by this protocol

         12. is able to demonstrate the willingness to participate by signing and understanding an
             informed consent after full explanation of the study

        Exclusion Criteria:

        Subject

          1. has a history of serotonin syndrome.

          2. 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 (ie. pathology of
             the salivary glands such as viral or bacterial sialadenitis or obstructive
             sialadenitis or Sjögren's Syndrome)

          3. is of childbearing potential and not using adequate contraceptive measures

          4. has history of retinal, basilar or hemiplegic migraine, cluster headache, or secondary
             headaches (such as due to trauma, infection, alterations of homeostasis, ear, nose and
             throat (ENT) or psychiatric disorders, cranial or cervical disorders or neuralgias)

          5. 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)

          6. has blood pressure equal to or greater than 160/90 millimeters of mercury (mmHg) in 2
             out of 3 blood pressure (BP) measurements at screening or is taking any
             angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker

          7. 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

          8. 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

          9. 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

         10. has a history of impaired hepatic or renal function that, in the investigator's
             opinion, contraindicates participation in this study

         11. has hypersensitivity, intolerance, or contraindication to the use of any triptan,
             non-steroidal anti-inflammatory drug (NSAID) or aspirin (including all sumatriptan and
             naproxen preparations) or has nasal polyps and asthma

         12. 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 (eg. Perimenstrual use of
             triptans and estradiol patches)

         13. 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. Overuse is defined as an average of 10 days per month over the
             last 6 months.

         14. 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.

         15. is currently taking and plans to continue an oral steroid any time from screening
             through onset of menses that will be treated with study medication (at the discretion
             of the investigator)

         16. has history of any bleeding disorder or is currently taking any anti-coagulant or any
             antiplatelet agent.

         17. has evidence or history of any gastrointestinal surgery or gastrointestinal (GI)
             ulceration or perforation in the past six months, gastrointestinal bleeding in the
             past year; or evidence or history of inflammatory bowel disease

         18. is pregnant, actively trying to become pregnant, or breast feeding

         19. 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.

         20. 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.