Real-world Data Analysis of REN Treatment in Adolescence With Migraine

Study Overview
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Brief Summary
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This is a Post-marketing study investigating the safety and efficacy of the REN device (Nerivio by Theranica, ISRAEL) in adolescents with migraine. Data analysis concerning the REN treatment efficacy in terms of pain and functional disability as a standalone treatment or in combination with other medications will be performed.

Detailed Description
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The REN device (Nerivio by Theranica, ISRAEL) is a neuromodulation device approved by the FDA for acute treatment of migraine in patients of 12 years old and above (1-4). It is a wearable device applied to the upper arm. It stimulates C and Aδ noxious fibers using a modulated, symmetrical, biphasic, square pulse with a pulse width of 400 μs, modulated frequency of 100-120 Hz, and up to 40 mA output current which the patient can adjust. The REN device is operated by a designated app that is downloaded to the user's phone prior first use of the Nerivio device As part of the sign-up process to the Nerivio app, all patients accept the terms of use which specify that providing personal information is done of their own free will and that their de-identified data may be used for research purposes. Users are not obligated to provide personal information and could treat without providing any feedback. The app includes a secured, personal migraine diary, which enables patients to record and track their migraines and other headaches. At the beginning of each treatment, and again 2 hours after the start of treatment, patients are prompted to record their symptoms, including pain level (none, mild, moderate, severe), functional disability (No limitation, Some limitation, Moderate limitation, Severe limitation), and an indication of which medications, if any, were taken within that 2-hour time window. Post-marketing surveillance is designed to assess the efficacy and safety in larger and more diverse populations and in various real-world environments and situations. As a digital therapeutic device (i.e., electroceutical), the REN device enables prospective collection of electronic patient-reported outcomes in real-world clinical practice. Recently, Real World Evidence (RWE) papers of Nerivio usage in adults were published (5-6). these papers demonstrated the safety and efficacy of the Nerivio device in a large-scale population using the accumulated data gathered by diary within the Nerivio app. This post-marketing RWE study investigates the efficacy of the Nerivio treatment using the following outcomes: - reduction in headache pain 2h post-treatment - improve in functional disability - A standalone treatment vs combination with other therapies - safety profile (in terms of device-related adverse events) Together, these four objectives provide a comprehensive evaluation of efficacy, drug-device interactions, dose stability, and safety, in a large real-world dataset of over XXXXX treatments in the migraine adolescent population.

Official Title
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Real-World Analysis of Remote Electrical Neuromodulation (REN) for the Acute Treatment of Migraine in Adolescence

Conditions
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Migraine in Adolescence

Intervention / Treatment
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* Device: Nerivio


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Age between 12-18 years - REN user across the United States who created Nerivio account on January 1st, 2021 or later. - Had at least two evaluable treatments with the Nerivio device Exclusion Criteria: (1) - Treatments shorter than 20 minutes

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Device: Nerivio|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.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Consistent Pain Relief at 2 Hours Post-treatment | The proportion of subjects reporting pain relief at 2 hours post-treatment without the use of rescue medication in at least 50% of all their treatments. Pain relief is defined as an improvement from severe or moderate pain to mild or no pain, Pain level is reported using a 4-point Likert scale (0 - No pain, 1 - Mild pain, 2 - Moderate pain,3- Severe pain) | 2 hours post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Consistent Pain Freedom at 2 Hours Post-treatment | The proportion of subjects reporting freedom from pain at 2 hours post-treatment without the use of rescue medication in at least 50% of all their treatments. Pain freedom is defined as reduction from severe or moderate or mild pain to no pain, Pain level is reported using a 4-point Likert scale (0 - No pain, 1 - Mild pain, 2 - Moderate pain,3- Severe pain) | 2 hours post treatment | 
| Consistent Usage of Migraine Abortive (Rescue) Medications | The proportion of subjects with REN treatments without the use of pharmacological migraine abortive (rescue) medication (either over the counter or prescribed) at 2 hours post-treatment in at least 50% of all their treatments. | 2 hours post treatment | 
| Consistent Functional Disability Relief at 2 Hours Post-treatment | The proportion of subjects reporting Functional Disability (FD) relief at 2 hours post-treatment without the use of rescue medication in at least 50% of all their treatments. FD relief is defined as an improvement from severe or moderate limitation to some or no limitation. FD level is reported using a 4-point Likert scale (0 - No limitation, 1 - Some limitation, 2 - Moderate limitation, 3 - Severe limitation) | 2 hours post treatment | 
| Consistent Functional Disability disappearance at 2 Hours Post-treatment | The proportion of subjects reporting no Functional Disability (FD) at 2 hours post-treatment without the use of rescue medication in at least 50% of all their treatments. FD disappearance is defined as an improvement from severe or moderate or limitation to no limitation. FD level is reported using a 4-point Likert scale (0 - No limitation, 1 - Some limitation, 2 - Moderate limitation, 3 - Severe limitation). | 2 hours post treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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migraine, Headache Nerivio, REN