Efficacy and Safety of Nerivio Device for Acute Treatment of Migraine in People With Chronic Migraine
Condition: Chronic Migraine
MeSH terms: Migraine Disorders
Study type: Interventional

Summary: 
      A prospective, single arm, open-label, multicenter trial to assess the efficacy and safety of
      the Nerivio device in chronic migraine patients. This study will be conducted in three
      phases:

      Phase I - Run-in:

      Eligible participants will be trained to use a smartphone migraine diary application. During
      the 4 weeks of this phase, participants will be instructed to report all their migraines and
      headaches at onset, 2 hours and 24 hours post report .

      Phase II - Treatment:

      A 4-week treatment phase in which participants will be asked to treat their migraine
      headaches with the Nerivio device and report it using the smartphone application at baseline,
      2 hours and 24 hours post-treatment.

      Phase III - Follow-up:

      An 8-week follow-up phase in which participants will incorporate the Nerivio device into
      their usual care according to their preference (Nerivio only, medication only, both or none).
      Participants will be asked to report all their migraines or headaches at onset, 2 hours post
      report and 24 hours post report.
    

Detailed description: 
      This open label study includes up to four visits. The enrollment and application training may
      occur in two separate visits instead of one.

      First visit - The first visit will include screening, enrollment and training on the
      application.

      Enrollment: The screening process will include an eligibility assessment and a urine
      pregnancy test. Following successful screening, the site staff will provide the participants
      with study related information, perform an enrollment interview and receive an informed
      consent from the participants. During this visit, participants will complete baseline
      questionnaires that included information on the frequency and severity of their migraine
      attacks, typical associated symptoms, use of preventive and acute treatments, and the effect
      that their migraine attacks have on their daily routine and quality of life.

      Application training: Eligible participants who enroll to the study will be trained to use
      the diary mode of the application that is installed on their own smartphones. The
      participants will be instructed to report the onset of all their migraines and headaches and
      complete a migraine diary questions regarding their pain intensity levels, the
      presence/absence of aura and associated migraine symptoms (nausea, photophobia, phonophobia,
      and allodynia) as well as rate their stress level and functional disability at baseline, 2-
      and 24-hours post-treatment. At the beginning of each treatment, participants will also be
      asked to report the time elapsed from attack onset. The site personnel will be required to
      document the training session in the Case Report Form (CRF).

      Run-in phase: After the enrollment visit, participants will undergo a 4-week migraine diary
      phase aimed to collect baseline migraine characteristics and further assess eligibility. The
      participants will use the app to record pain intensity levels, the presence/absence of aura
      and associated migraine symptoms (nausea, photophobia, phonophobia, and allodynia) as well as
      the effect that their migraine attacks have on their daily routine and quality of life, at
      baseline, 2- and 24-hours post-treatment. These reports will be transferred by the
      application to the electronic data capture (EDC) system, where they will be collected and
      registered.

      Participants who report at least 6 qualifying migraine headaches with pain data at baseline
      and 2 hours post-treatment will continue to the treatment phase.

      Second visit- Device training: Eligible participants who successfully complete the run-in
      phase will receive the Nerivio™ device. The device will be registered and connected by
      Bluetooth to their smartphone. During this visit, participants will be trained to use the
      device. Device training will include finding the optimal individual stimulation intensity
      level (perceptible but not painful), that will be subject to change during the treatment
      phase. The site staff will also carefully review with the patient how to identify a
      qualifying migraine headache (see below) and provide detailed instructions on study
      procedures.

      If the research staff recognizes that the participant cannot tolerate the feeling of the
      electrical stimulation, the participant may be withdrawn from the study.

      During the training, participants will also be informed on the key elements which are
      critical for the successful conduct of the study:

        -  Treatments of migraine and headaches with Nerivio™ should be performed as soon as
           possible after migraine headache or aura began and always within one hour of symptoms
           onset. Treatments of mild headaches are accepted.

        -  Avoid taking rescue medications within two hours post-treatment (2 hours from start of
           treatment), if possible.

        -  The treatment should be performed for at least 30 minutes (the recommended treatment
           duration is 45 minutes).

      The site personnel will be required to document the training session in the CRF.

      Treatment phase: Participants will be instructed to use the device for the treatment of
      migraine and/or headaches (see below) as soon as possible and always within 60 minutes of
      onset during a period of up to 4 weeks. Participants will be instructed to use the device
      with the intensity level identified during the device training visit (and adjust as
      necessary) and make sure the stimulation is perceptible but not painful. Participants will be
      instructed to avoid taking rescue medications within 2 hours post-treatment. If medications
      are used, participants will be instructed to record in the app when and which medication was
      taken at 2- and 24-hours post treatment. The participants will use the app to record pain
      intensity levels, the presence/absence of aura and associated migraine symptoms (nausea,
      photophobia, phonophobia, and allodynia) as well as the effect that their migraine attacks
      have on their daily routine and quality of life, at baseline, 2- and 24-hours post-treatment.
      At the beginning of each treatment, participants will also be asked to report the time
      elapsed from attack onset. Adverse events will be reported throughout this phase of the study
      directly to the site staff.

      Participants who do not achieve satisfactory relief at 2 hours post-treatment may treat again
      with the Nerivio™ device or may treat with usual care at that time or any time thereafter if
      the headache does not resolve. Participants will also be able to treat headache recurrence
      with the device. Migraine headaches that are not treated with the device may be treated with
      usual care.

      The first reported treatment will be considered a "training" treatment, aimed to verify that
      the participants use the device properly, and will only be included in the safety analysis.
      The efficacy evaluation will be performed on the first treatment of a qualifying attack (see
      below) following the training treatment (hereby termed "test treatment").

      Third visit- Follow-up phase:

      Following the 4-week period of the treatment phase, participants will return to the clinic to
      fill questionnaires assessing satisfaction and user experience. All participants who complete
      the treatment phase will enter an additional 8-week phase in which the device can be
      incorporate into their usual care. Participants will treat their migraines and headaches
      according to their preference- treatment with Nerivio only, treatment with medication only,
      both treatment options, or none. Participants will be asked to report all their migraine
      headaches at onset (migraines or headache), regardless if they are using the device or not.
      The participants will use the app to record pain intensity levels, the presence/absence of
      aura and associated migraine symptoms (nausea, photophobia, phonophobia, and allodynia) as
      well as the effect that their migraine attacks have on their daily routine and quality of
      life, at baseline, 2- and 24-hours post-treatment.

      Fourth (final) visit - End of study:

      Participants will return to the clinic following the end of the follow-up phase, at which
      time they will return the device. The participants will have the option of returning the
      device by mail instead of an on-site visit. Participants may be asked to fill additional
      questionnaires on their migraine and their experience with the device.
    

Intervention name(s): Nerivio
Intervention type(s): Device
Intervention description(s): A remote electrical neuromodulation (REN) device for the acute treatment of migraines.The device delivers transcutaneous electrical stimulation to the upper arm to induce conditioned pain modulation (CPM) that activates a descending endogenous analgesic mechanism. The treatment is self-administered and controlled by a smartphone application.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment