Sumatriptan as Treatment for Post-traumatic Headache
Condition: Post-traumatic Headache
MeSH terms: Post-Traumatic Headache; Headache
Study type: Interventional
Phase: Phase 2

Summary: 
      This phase II evaluation of sumatriptan as a treatment for post traumatic headache (PTH) will
      examine the methods and approach necessary to take the next step to a phase III trial. The
      sample will include 40 persons with mild complicated, moderate or severe TBI who will be
      recruited from patients discharged from the acute rehabilitation unit as well as outpatient
      clinics and the community who are between 3 and 24 months of injury and will be followed over
      3 months. The investigators plan to enroll those who have moderate to severe headache with
      frequency of at least four and up to a maximum of fifteen total headache days per month and
      at least three months after discharge from hospital. The investigators will use headache
      diaries to track the headaches for a month. If subjects still have significant headache, the
      investigators will instruct them in the use of sumatriptan 100 mg. to treat headaches. The
      subjects will continue to keep daily headache diaries. The investigators will evaluate them
      at baseline, Day 30 and Day 90. Each subject will receive weekly telephone follow up calls
      from the research staff. The investigators will measure pain severity, duration, recurrence
      of headaches, and side effects and how well persons with TBI can use headache diaries.
    

Detailed description: 
      I. Specific Aims of Study: The ultimate aim of this Phase II open-label study is to test the
      research methods and approach necessary to successfully carry out a Phase III study for the
      treatment of post-traumatic headache (PTH). During this study, we will

        1. Determine the feasibility of using a headache diary accessed via smart phone
           application, the web, or paper/pencil to record accurate headache data in a group of
           individuals with TBI, and their caregivers as indicated.

        2. Evaluate the approximate effect size of sumatriptan on pain severity, duration, and
           recurrence of headaches in persons with moderate to severe PTH in order to establish the
           necessary sample size for a Phase III study.

        3. Assess the side effect profile of sumatriptan in a brain-injured population as well as
           the safety of sumatriptan in subjects with TBI.

        4. Evaluate the ability of persons with TBI, and their caregivers as indicated, to
           successfully use abortive headache medications and comply with treatment.

        5. Examine the relationship between PTH and cognitive, emotional, and other self-report
           measures to determine important factors to include in a Phase III study.

      This is a single arm, unblinded study enrolling 40 subjects and is being undertaken to test
      necessary study instruments and procedures, establish feasibility and determine side effects
      in a population with mild complicated, moderate or severe TBI in preparation for a subsequent
      Phase III study.

      Data collection will occur at enrollment (Clinic Visit 1) at which baseline testing will
      occur, Day 30 (Clinic Visit 2), and Day 90 (Clinic Visit 3).

      Pre-treatment Visit (Visit 1): Subjects who complete informed consent and meet the inclusion
      criteria (with no exclusion criteria) will be asked to complete 30 days of headache diary to
      document the number of headaches, headache severity, headache days and description of their
      headache and associated symptoms. Research staff will contact them on a weekly basis to
      answer questions and maximize accuracy and compliance with the diary. Proper utilization of a
      headache diary and success of data input by the subject and caregiver will be evaluated
      following weekly interviews with the research assistant.

      Treatment Visit (Clinic Visit 2):

      A medical history will be obtained to review inclusion and exclusion criteria and to elicit a
      thorough review of systems so that adverse events will be identifiable if they occur.
      Physical examination will also ensure that cardiovascular status is compatible with
      sumatriptan use and will document current status to allow for identification of potential
      adverse events. Finally, standard primary headache classification criteria will be reviewed
      with each patient to determine whether they meet criteria for migraine or probable migraine.
      Headache histories will be assessed and subjects that have experienced between 4-15 headaches
      will be included in the medication intervention with Sumatriptan. Subjects who qualify for
      the Sumatriptan intervention will receive several assessments, given medication, usage
      instructions, and scheduled for weekly phone calls for weeks 5-11. Individuals whose
      headaches do not meet criteria for migraine or probable migraine, based on data from headache
      diaries, will have their participation in the study end.

      Weekly Telephone Follow-Up Calls: Research staff will call each participant weekly to check
      on compliance with drug diary use during the first month of the study (Weekly calls 1-3) to
      check on compliance in diary usage. For weekly calls in weeks 5-11 (for the intervention
      participants), research staff will inquire about study drug usage, and query for adverse
      events. Use of rescue medications for headache will be recorded. In the case of minor adverse
      effects which are bothersome to the patient, the dosage will be decreased by ½ pill per use.

      Follow up Visit (Visit 3). This will be the final visit for the subjects. Vital signs will be
      obtained. Drug containers and headache diaries will be collected from all subjects. Outcome
      measures will be administered.

      Use of sumatriptan and rescue drug: Two packages of nine (9) sumatriptan 100- mg. pills (18
      pills total for 2 months of treatment) will be dispensed to each subject on Day 30 once they
      have gone through baseline assessment. On average, this will treat a minimum of 5 headaches
      or a maximum of 9 headaches per month. Subjects will be instructed to take the sumatriptan at
      the onset of headache pain. If subjects are not pain free at 2 hours after the first dose of
      study medication, they will be allowed to take one additional pill, but will be limited to 2
      pills in a 24 hour period. Subjects will be instructed to take no more than 9 pills in a 30
      day period based on research which suggests that additional dosages may increase the risk of
      medication-overuse headache. A list of appropriate medications will be provided that they can
      use if they: 1) continue to have headache pain 2 hours after their second dose of study drug,
      or 2) they have used their 30 day supply of study drug within the month. All subjects will be
      contacted by telephone on a weekly basis to review their headache diaries, assess potential
      adverse events, review compliance with use of the study drug, assess other treatments being
      utilized, and answer any questions.

      Data Analysis: Data analysis for the feasibility and safety aims will be primarily
      descriptive. The investigators will calculate the percent of subjects who used the diary
      successfully, percent who stopped taking sumatriptan because of side effects, percent who
      experienced each adverse event, and percent who were able to maintain compliance with
      treatment. A confidence interval will be determined for each estimate. To get preliminary
      data on efficacy of sumatriptan, headache control will be compared before and after the
      participants start taking sumatriptan. The investigators will calculate the percent of
      headaches that had complete resolution (pain free at 2 hours) for each person, during the
      initial (pre-intervention) month when they used their regular treatment and during the two
      months (intervention) when they treated headaches with sumatriptan and compare them using a
      paired t-test. The investigators will also examine different definitions of headache relief
      (pain free by 30 minutes, no more than mild pain (score <=1) by 30 minutes, no more than mild
      pain by 2 hours) to see if another outcome measure may have advantages for a future Phase III
      study. Any differences in compliance, side effects, and feasibility based on cognitive
      functioning will be described, as well as by other self-report and emotional health measures.
      Changes in these measures from pre to post treatment will also be examined to determine
      whether there is any change that occurs with treatment and which may be important variables
      to include in a Phase III study.
    

Intervention name(s): Sumatriptan 100 mg
Intervention type(s): Drug
Intervention description(s): This is a single-arm, unblinded study of treatment for post-traumatic headache with the open label medication sumatriptan and is being undertaken to test necessary study instruments and procedures, establish feasibility and determine side effects in a population with complicated mild, moderate and severe TBI.
Other intervention name(s): Imitrex; Imigran
Intervention MeSH terms: Sumatriptan
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Post-traumatic headache; Traumatic brain injury; Sumatriptan