Assessment of Safety and Efficacy of Nerivio for the Migraine Prevention
Condition: Migraine
MeSH terms: Migraine Disorders
Study type: Interventional

Summary: 
      Migraine is a common neurologic with attacks of headache and associated symptoms such as
      nausea, vomiting, phono and photophobia. Migraine can lead to substantial functional
      impairment. This study intends to demonstrate the safety and efficacy of the Nerivio for
      migraine prevention.

      The study is a prospective, randomized, double-blind, sham-controlled, multicenter study,
      conducted in three phases.

      The study will consist of a screening/enrollment visit, followed by a 4-week (28 days)
      baseline phase, an 8-week double-blind preventive treatment phase, and a 4-week open-label
      phase.

      Patients will complete an electronic diary throughout the study; this includes a daily
      evening report (completed regardless of whether the patient had a headache) and treatment
      feedback during the follow-up pre-emptive phase.

      The primary endpoint is the mean change in the average of migraine headache days per month
      comparing the 4-week baseline phase (weeks 1 through 4) with the last 28 days of the
      treatment phase (weeks 9 through 12).
    

Detailed description: 
      Nerivio is a neuromodulation device approved for the acute treatment of migraine with or
      without aura in patients 12 years of age or older. The device utilizes electro stimulation to
      achieve conditioned pain modulation (CPM). CPM stimulate endogenous analgesic mechanism.
      Treatments are self-administered by the user at the onset of a migraine attack. this study
      intends to demonstrate the safety and efficacy of the Nwrivio for migraine prevention.

      The study is a prospective, randomized, double-blind, sham-controlled, multicenter trial,
      conducted in three phases. The ratio between treatment and control groups will be 1:1,
      stratified by center and patient type (chronic/non-chronic). The study will consist of a
      screening/enrollment visit, followed by a 4-week (28 days) baseline phase. Eligible
      participants will enter an 8-week double-blind preventive treatment phase. Following the
      preventive treatment phase, patients will be offered to participate in a 4-week open-label
      pre-emptive treatment phase or continue their prevention treatment with an active device,
      according to their eligibility.

      Patients will complete an electronic diary throughout the study; this includes a daily
      evening report (completed regardless of whether the patient had a headache) and treatment
      feedback during the follow up pre-emptive phase

      Phase I - Baseline - 4 weeks (weeks 1 through 4):

      Eligible participants will install the Nerivio app on their smartphones and will be
      instructed to record daily their migraine/headaches symptoms and medication use on the
      Nerivio app.

      Transition to the treatment phase: Participants who meet the following criteria in the
      baseline phase will be eligible to continue to the treatment phase:

        -  Complete the diary in at least 22 out of the 28 days during the baseline phase (80%)

        -  Have between 6 to 24 headache days during the 28-day baseline period

        -  At least 4 of their headache days during the baseline phase fulfill the International
           Classification of Headache Disorders 3rd edition (ICHD-3) criteria for migraine
           (migraine without aura [code 1.1; C and D] or with aura [code 1.2; B and C], or probable
           migraine, or headaches requiring the use of migraine-specific medications including
           triptans, gepants or ergot derivatives).

      Phase II - treatment phase (prevention) - 8 weeks (weeks 5 through 12):

      Participants who meet the baseline phase requirements will be randomized in a 1:1 ratio to
      active and sham groups. Participants will be instructed to complete a daily diary (in the
      Nerivio app) about their headaches, associated symptoms, and medication use. They will also
      be instructed to conduct a 45-minute treatment with Nerivio every other day.

      Transition to the follow-up phase (open label):

      At the end of the treatment phase, participants from both arms (active and sham) may continue
      to a follow-up phase in which they will receive an active device that can be used during this
      phase. The data of all participants will be used for safety analyses.

      The data of participants from the baseline and treatment phases will be used to assess their
      eligibility to participate in the pre-emptive follow-up phase. Participants eligible for the
      follow-up phase meet the following conditions:

        -  Between 6-16 headache days during the baseline phase.

        -  Participants experience prodrome symptoms within 24 hours prior to the onset of their
           migraine headache in at least half of their migraine attacks during the baseline phase.

        -  Participants completed the daily questionnaires in at least 70% of the days during the
           treatment phase.

        -  Treated every other day in at least 24 and less than 33 days during the 56 days of the
           treatment phase.

      All adverse events will be reported.

      Phase III - Follow-up phase (open label) - 4 weeks (weeks 13 through 16):

      All participants will receive an active Nerivio device to use during the follow-up phase.
      Participants who do not meet the above requirements will be able to enter into the safety
      follow-up and continue to use Nerivio every other day for the preventive treatment of
      migraine. They will be instructed to compete a daily diary as was done in the treatment
      phase.

      Participants who meet the above requirements will enter the pre-emptive follow-up phase and
      be instructed to conduct a 45-minute device treatment within 60 minutes of prodrome symptom
      onset. Participants will be instructed to complete questionnaires regarding their headache,
      prodrome symptoms, and medication use at baseline (start of treatment), 2 hours
      post-treatment, and 24 hours post-treatment. In addition, participants will be instructed to
      continue to report the daily diary, as performed in the other phases of the study.

      All adverse events will be reported.
    

Intervention name(s): Nerivio active device; Nerivio sham device
Intervention type(s): Device; Device
Intervention description(s): Nerivio neurostimulator of conditional pain modulation (CPM); Nerivio neurostimulator with an electrical output not intended for neurostimulation
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized, double-blind, sham-controlled
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Prevention