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
Study type: Interventional
Phase: Phase 4

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™.
    

Detailed description: 
      This double-blind multi-site study will be conducted to enroll 40 evaluable participants. All
      subjects will be medically stable at enrollment and be on a stabilized dosage of daily
      medications.

      At Visit 1 (Baseline) following Informed Consent, a physical and neurological exam, baseline
      electrocardiogram (ECG), and vital signs will be completed. A urine pregnancy test will be
      collected by all subjects of childbearing potential. Routine labs (electrolyte panel with
      creatinine, alanine aminotransferase (ALT) / aspartate aminotransferase (AST), a luteinizing
      hormone (LH) lab (for menstrual cycle staging) and a baseline saliva sample (for CGRP,
      estrogen, cortisol, VIP, a-amylase, PGI2, PGE2 and β-endorphin analysis) will be collected.
      Subjects should be headache-free at Visit 1. A medical, headache, and medication history will
      be collected on all subjects and eligible subjects will be randomized 1:1 to Group A or Group
      B. Group A will receive Treximet™ (sumatriptan succinate 85 milligrams (mg) and naproxen
      sodium 500 mg) 1 tablet. Group B will be provided 1 matching placebo tablet. Subjects will be
      instructed to not start study medication until notified by study staff that lab results were
      normal and they are eligible to proceed. Subjects will be instructed to treat as early as
      possible following the onset of a typical menstrual headache. Groups A and B will be provided
      with Treximet™ 1 tablet for rescue between 2 and 24 hours for persistent or recurring
      headache. Subjects will receive a Diary and instructions on Digital Versatile Disc (DVD)
      regarding documentation. Migraine associated symptoms (ie nausea, vomiting, light
      sensitivity, or sound sensitivity) will be collected as well as sleeplessness, difficulty
      thinking other bodily pain, and menstrual associated symptoms (to include intensity of
      menstrual cramps).

      Subjects will be given kits with written instructions for collection of urine and saliva
      samples and additional saliva instructions on DVD. All subjects will be given LH testing kits
      to define the time of ovulation. Diary documentation begins at the time of ovulation. They
      will collect baseline saliva and first morning urine samples during the mid-luteal time
      period for two consecutive days, which is defined as 4-7 days after the LH surge. Subjects
      will also be instructed to begin collection of saliva 48 hours prior to the start of menses
      at 8:00 am, 2:00 pm, and 8:00 pm for two days or until menstrual migraine occurs. They also
      will collect a first morning urine sample on the two mornings prior to menses. At the point
      of headache onset, subjects will be instructed to collect saliva at onset of pain, time of
      treatment, 2 and 24 hours following treatment, at pain free, 2 hours after pain free, and 24
      hours after pain free. Subjects will also be instructed to collect a urine specimen when they
      are pain free following treatment with study medication. Subjects will document migraine
      associated symptoms, menstrual associated symptoms, and recurrence symptoms at all saliva
      collection time points in the provided Diary per instruction.

      Subjects should be instructed to phone the study coordinator at the end of the menstrual
      cycle to return for Visit 2 within 7 days.

      _________________________

      At Visit 2 (Review) Diaries will be reviewed and frozen saliva and urine samples will be
      returned to the clinic. Subjects must meet the following criteria for urine and saliva
      analysis:

        -  Diary review indicates that headache would have, if left untreated, at least one symptom
           of migraine (nausea, vomiting, phonophobia, or photophobia) . And

        -  Headache was associated with the onset of menses

      And

      • Saliva and urine samples are returned to the clinic.

      Medical and medication history will be updated and adverse events collected. A urine
      pregnancy test will be collected by all subjects of childbearing potential. Drug
      accountability and compliance will be assessed.
    

Intervention name(s): Treximet; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Tablet for oral administration contains sumatriptan 85mg / naproxen sodium 500mg.; A placebo tablet matching Treximet for oral administration.
Other intervention name(s): Sumatriptan/Naproxen Sodium
Intervention MeSH terms: Naproxen; Sumatriptan
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Menstrual migraine; Menstrually-related migraine; Treximet; CGRP; calcitonin gene-related peptide