Evaluation of a Novel Device for Treatment of Migraine Headache
Condition: Migraine Without Aura; Migraine With Aura
MeSH terms: Migraine Disorders; Migraine without Aura; Migraine with Aura
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.

      Recent evidence suggests that electro stimulation is effective in providing relief for
      chronic headaches including migraine. It is tolerable by patients and associated with no
      adverse effects.

      The device utilizes electro stimulation to achieve conditioned pain modulation (CPM). CPM an
      stimulate endogenous analgesic mechanism. The modulatory effect is over the whole body, and
      can be induced anywhere.

      This is a prospective, randomized, double-blind, sham controlled multi-center trial. Ratio
      between treatment and control groups will be 1:1, stratified by center and use of preventive
      medications.

      The study objectives is to demonstrate the safety and effectiveness of the Nerivio Migra
      electro stimulation device for the reduction of migraine headache during an attack of
      migraine with or without aura.

      The study is intended for subject with 2-8 migraine episodes per month. patients will receive
      the device, either an active or a placebo type, and will be asked to use the device at home
      or in any location that they will be when the migraine starts.

      The study hypothesis is that electro stimulation delivered transcutaneously to the peripheral
      nervous system at onset of a migraine attack significantly reduce headache pain demonstrated
      by a significant difference between proportions of responders to the active treatment
      stimulation in comparison to proportion of responders that will use a placebo device.
    

Detailed description: 
      Nerivio Migra is intended for the acute treatment of migraine with or without aura in
      patients 18 years of age or older. It is self-applied to the upper arm. Treatments are
      self-administered by the user at the onset of a migraine attack. The device delivers extra
      cephalic transcutaneous electrical stimulation below the pain threshold to the skin of the
      upper arm at the onset of a migraine attack. Nerivio Migra is operated via a mobile
      application.

      This is a prospective, randomized, double-blind, sham controlled multi-center clinical trial
      to test the ability of the Nerivio Migra neuromodulation device to relieve the patient's
      migraine pain during a migraine attack. The study will enroll up to 270 patients diagnosed
      with migraine with or without aura, per the inclusion and exclusion criteria. These patients
      will be individually and randomly assigned to either treatment group or control group. For
      sham control, electrical pulses of similar width and intensity, but much lower frequency
      compared to the active device will be administered. This sham program produces pulses that
      are perceivable by the user, thus maintaining the blinding, but on the other hand do not have
      therapeutic qualities, based on existing knowledge of parameters range of electro stimulation
      treatments.

        1. st visit - screening, enrollment and training on the application in diary mode Following
           successful screening, enrollment interview and signing of informed consent, participants
           will be provided with the Nerivio Migra application (either installed on their own
           smartphone, or on a smartphone provided by the study coordinator). The participants will
           be trained how to operate the application and report their migraine attacks in the
           patient diary mode, which is part of the application. The site personnel will be
           required to approve the training session in the CRF.

           Stage 1 - Roll in phase The Roll-in is a period of 15 - 30 days in which at least two
           (2) and no more of eight (8) migraine attacks has been occurred. During this period,
           baseline information including mean frequency and severity of migraine attacks,
           occurrence of other headaches, presence of ICHD-3 diagnostic criteria for migraine with
           or without aura and use of preventive and rescue medications will be recorded.

        2. nd visit Following the Roll-in phase, the participants will arrive to the clinic and
           their compliance to the study procedures and eligibility to continue to the next phase
           will assessed.

      Participants that will be eligible to continue to the treatment phase will undergo the
      following:

        1. Participant will be randomized into one of the two study group (Active or Sham device)
           Investigational devices will be programmed in active or sham mode with a 1:1 ratio, in
           order to achieve the desired ratio between active and control groups sizes, stratified
           with by use of preventive medications.

        2. Participant will be trained on the device, the application (in diary and treatment
           modes), the treatment procedures and the key elements critical for the success of the
           study:

             -  Apply the Nerivio Migra as soon as possible following the onset of the migraine
                symptoms and NO LATER than 60 min from onset

             -  Refrain from taking any rescue medication 2 hours following the start of treatment.

             -  Perform the treatment for a period of at least 30 minutes (recommended treatment
                time is 45 minutes).

      Stage 2 - Parallel arms, double- blind treatment phase. Participants will be instructed to
      activate the device at onset of a qualifying migraine attack and manually adjust stimulation
      intensity to a level within the pre-defined range, where it is well perceived but not
      painful. A qualifying migraine attack shall be preceded by at least 48 hours of freedom from
      migraine. Patients will be requested to refrain from use of rescue medications prior to and
      during the first two hours after treatment with the device, and if they cannot comply with
      this, record their use of rescue medications (migraine specific drugs or other medications or
      therapies that may be used to treat pain, from a pre-specified list) in the mobile
      application.

      Via the smartphone application, each participant will be asked to rate his/her migraine pain
      level three times using Pain Grades Scale (0 - no pain, 1- mild pain, 2- moderate pain, 3 -
      severe pain): (1) upon starting the treatment, (2) two hours after start of treatment, (3) 48
      hours after start of attack. At the start of each treatment, participants will be also asked
      to provide time elapsed from start of migraine symptoms to start of the treatment.
      Participants will be also asked to provide feedback regarding their use of medication
      (migraine specific drugs or other medications or therapies that may be used to treat pain,
      from a pre-specified list), presence of nausea, photophobia, phonophobia or allodynia, and
      treatment perception. After providing feedback at two hours after start of treatment and in
      case of pain recurrence, participants will be allowed to re-treat the attack using Nerivio
      Migra device.

      Adverse events will be reported.

      Stage 3 (optional, by subject request only) - Open label extended treatment:

      Following the completion of double-blind stage of the study, all subjects will be offered a
      2-month open label period using the active device.
    

Intervention name(s): Nerivio Migra-1 active device; Nerivio Migra-1 Sham device
Intervention type(s): Device; Device
Intervention description(s): The device is placed on the subject upper arm. when activated, stimulus is applied to influence the subject's perception of a painful stimulus, delivered (or originating) at a different location. Based on diffused noxious inhibitory control mechanism, sometimes referred to as "pain inhibits pain" principle, conditioned pain modulation evokes an endogenous analgesic mechanism. The modulatory effect is over the whole body, and can be induced anywhere in the body. This approach allows applying the conditioning stimuli away from the painful site.; The device is placed on the subject upper arm. when activated, the stimulus is applied is not sufficient to influence the subject's perception of a painful stimulus.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: A prospective, randomized, double blinded, sham controlled study
Masking: Double (Participant, Investigator)
Primary purpose: Treatment