Caffeine/Propranolol Intervention for Acute Migraine
Condition: Migraine Disorders
MeSH terms: Migraine Disorders
Study type: Interventional
Phase: Phase 2

Summary: 
      This is a research study to assess the safety of caffeine/propranolol at different dose
      levels. We want to find out what effects, good and/or bad, it has on patients and their
      migraines.
    

Detailed description: 
      There will be a screening exam to find out if potential subjects are eligible to be in the
      main part of the study. Screening will include obtaining demographics, migraine history,
      migraine characteristics, verification that subjects's migraine satisfies the International
      Headache Society criteria, migraine medication history with success and failure rates, and
      medical history.

      If a subject is female, we will need to confirm to the extent medically possible that they
      are not pregnant. Female subjects must agree to have a urine pregnancy test done before
      beginning this research study. If a subject is a woman who is able to become pregnant, it is
      expected that they will use an effective method of birth control to prevent exposing a fetus
      to a potentially dangerous agent with unknown risk. They must accept the risk that pregnancy
      could still result despite the responsible use of reliable method of birth control.

      They agree to notify Dr. Cho as soon as possible of any failure of proper use of your birth
      control method, or if you become pregnant, either of which may result in your being withdrawn
      from the study.

      Subjects will also undergo a liver function test as well as an EKG to make sure they are
      eligible for the study.

      Once subject eligibility has been determined, they will be randomized to one of 3 study
      groups described below. Neither the subjects nor the doctor can choose which group subjects
      will be in nor will subjects or their doctor know which group subjects are in. They will have
      a one in three chance of being placed in any group. Two groups will be active treatment with
      either 400 mg caffeine and 40 mg propranolol or 1000 mg caffeine and 40 mg propranolol. The
      third group will be a placebo group with no active medication.

      Subjects will then be given a study kit, which includes caffeine/propranolol or placebo oral
      medication, a treatment booklet, migraine headache diary, pen and stopwatch. The study
      coordinator will then instruct them in the accurate method of diary completion and use of the
      oral medication or placebo pill. Their final visit will be scheduled within 60 days of
      enrollment.

      They will be instructed to treat one moderate or severe migraine attack with the study
      medication. They will be instructed to take study medication at aura onset in the presence of
      another adult.

      In the absence of any aura, they will be instructed to take study medication at headache
      onset. Another adult should be present when taking the study medication to ensure safety. In
      the event that the migraine occurs while they are alone, the subjects are instructed not to
      take the study medication and to wait for the next headache when adult supervision is
      available. They will not be allowed to use any non-steroidal,anti-inflammatory drugs such as
      ibuprofen or naproxen sodium, non-prescription analgesics such as acetaminophen or aspirin,
      narcotic analgesics such as oxycontin, oxycodone, triptan or ergotamine medication or
      derivatives (Cafergot®, D.H.E., 45®[dihydroergotamine mesylate], Efcaf®, Ergomar®, Ergostat®,
      Migranal®, Nasal Spray, Sansert®[methysergide], or Wigraine®) within 24 hours prior to dosing
      with the study medication. Subjects will also be instructed not to use any caffeine such as
      coffee, tea, caffeine containing sodas, or caffeine containing medications (Cafcit®,
      Caffedrine®, Enerjets, Lucidex, No Doz® Maximum Strength, Vivarin®) within 6 hours prior to
      dosing with the study medication.

      Subjects will record the severity of their headache and associated symptoms at baseline and
      15, 30, 45, 60, and 120 minutes after dosing. If the migraine does not resolve or worsens
      after 2 hours, they will be allowed to take #rescue medication# as prescribed by their
      physician. Subjects will continue to record the severity of their headache and associated
      symptoms for 4, 12, and 24 hours after initial dosing. Following the last entry in the
      subject diary at 24 hours, they will be asked to complete a treatment satisfaction
      questionnaire. They will also be asked to contact Dr. Cho#s office to review their diary
      completion and to confirm the date of their final visit.

      If subjects have not called to report a migraine within a month (±7 days) of enrollment, Dr.
      Cho or someone from his research staff will call them to determine if they have treated a
      migraine. If a migraine was treated, Dr. Cho or the study staff will interview them to
      determine if the diary has been appropriately completed and to ensure that adequate
      information has been recorded. Their final visit will be confirmed and should occur within 30
      days of the treated migraine. If they have not treated a migraine with the study medication
      within the first 30 days of enrollment, their final visit will be rescheduled within 60 days
      of your enrollment date (± 7 days).

      At the final visit, the study coordinator will review their subject diary for completeness
      and accuracy. All study materials will need to be returned at this visit. Subjects will then
      have a second EKG to make sure the medication didn't have any negative effects on their
      cardiac function. Subjects will be given a voucher to pay for parking expenses. In addition,
      there will be a data safety monitoring unblinding event after the first 15 patients have
      completed the study. All serious and non-serious adverse events will be analyzed regardless
      of the investigators' assessments of causality. Adverse events that result in death,
      hospitalization, permanent disability or threat to life are classified as serious. The
      Medical Dictionary of Regulatory Activities (MedDRA) will be used to categorize reported
      adverse events. Someone who is not directly related to the research team will conduct the
      safety monitoring.

      If there are any serious adverse events during the study, the study will be discontinued.
    

Intervention name(s): caffeine/propranolol combination tablet; placebo
Intervention type(s): Drug; Drug
Intervention description(s): caffeine/propranolol combination tablet administered orally once daily; placebo to match caffeine/propranolol combination tablet administered orally once daily
Intervention MeSH terms: Propranolol; Caffeine
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment