Migraine With and Without Aura Characteristics and Response to Remote Electrical Neuromodulation (REN) Treatment

Comparison of Migraine With and Without Aura in a Large Cohort: Characteristics and Response to Remote Electrical Neuromodulation (REN) Treatment

This is a Post-marketing, real-world evidence study investigating the safety and efficacy of the acute treatment of migraine with a Remote Electrical Neuromodulation (REN) device (Nerivio) in migraine patients with and without aura, as well as characterizing demographic and attack characteristic differences between migraine patients with and without aura.

Safety will be assessed by the number and type of device-related adverse events. Efficacy will be evaluated as a change in headache pain severity from baseline to 2 hours post-treatment. Disease characteristics will look into demographic and attack differences between patients with and without aura.

Study Overview

• Status: Completed
• Conditions: Migraine Without Aura; Migraine With Aura
• Intervention / Treatment: Device: Nerivio device

Detailed Description

The REN device (Nerivio by Theranica, Israel) is a neuromodulation device approved by the FDA for acute and/or preventive treatment of migraine in patients 12 years old and above. It is a wearable device applied to the upper arm.

As part of the sign-up process for the Nerivio app, all patients accept the terms of use which specify that providing personal information is done on 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 the presence or absence of aura, pain level (none, mild, moderate, severe), functional disability (none, mild limitation, moderate limitation, severe limitation), presence of associated symptoms (photophobia, phonophobia, and nausea), and an indication of which medications, if any, were taken within that 2-hour time window.

This post-marketing RWE study investigates the safety and efficacy of the Nerivio treatment in patients with and without aura by analyzing data from patients who used the Nerivio device. The following outcomes will be assessed:

1. Migraine clinical characteristics - Headache pain severity, functional disability and presence of associated symptoms at treatment baseline.
2. Consistent efficacy - Pain relief, freedom from pain, functional disability relief, return to normal function (no disability) and freedom from associated symptoms at 2 hours post-treatment relative to baseline in at least 50% of the treatments.
3. Safety - Rate of serious adverse events, and device-related adverse events in the study's period.

Together, these objectives provide a comprehensive evaluation of the effect of REN as a treatment for migraine with or without aura.

• Study Type: Observational
• Enrollment (Actual): 31715

Contacts and Locations

Study Locations

• Israel
  • Netanya, Israel, 4520438
    • Theranica Bio-Electronics ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients who were diagnosed with migraine by their HCP and were prescribed Nerivio for treatment of acute migraine

Description

Inclusion Criteria:

• Users aged 8 years old and above
• Users who treated their migraine attacks with the Nerivio device at least twice
• Users who prospectively reported the presence of aura in at least two treatment reports (reporting at least twice having aura) , OR:
• Users who prospectively reported the absence of aura in all of their reports, with at least two reports

Exclusion Criteria:

• Users who prospectively reported having aura only once

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Migraine with aura (MWA); Patients with migraine who treated their migraine attack with the Nerivio device at least twice and reported having aura in at least two treatment reports	Device: Nerivio device; REN treatment with Nerivio device
Migraine without aura (MWoA ); Patients with migraine who treated their migraine attack with the Nerivio device at least twice and reported the absence of aura in all of their reports, with at least two reports	Device: Nerivio device; REN treatment with Nerivio device

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of consistent Headache Relief at 2 Hours Post-treatment between the MWA and MWoA groups	The difference between the MWA and MWoA groups in the proportion of subjects reporting headache relief at 2 hours post-treatment in at least 50% of all their treatments. Headache relief is defined as an improvement from severe or moderate pain to mild or no pain.	2 hours
Comparison of Headache Severity at treatment baseline (T=0h) between the MWA and MWoA groups	The difference between the MWA and MWoA groups in the proportion of subjects reporting severe/moderate headache pain in at least 50% of their attacks.	0 hours (at baseline)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of consistent Pain Freedom at 2 Hours Post-treatment between the MWA and MWoA groups	The difference between the MWA and MWoA groups in the proportion of subjects reporting pain freedom at 2 hours post-treatment in at least 50% of all their treatments. Pain freedom is defined as the disappearance of pain from severe, moderate, or mild at treatment initiation to no pain 2 hours later.	2 hours
Comparison of Functional Disability at treatment baseline (T=0h) between the MWA and MWoA groups	The difference between the MWA and MWoA groups in the proportion of subjects reporting severe/moderate disability in at least 50% of their attacks.	0 hours (at baseline)
Comparison of Photophobia, Phonophobia and Nausea/vomiting presence at treatment baseline (T=0h) between the MWA and MWoA groups	The difference between the MWA and MWoA groups in the proportion of subjects reporting presence of a specific symptom in at least 50% of their attacks.	0 hours (at baseline)
Comparison of Consistent Functional Disability Relief at 2 Hours Post-treatment between the MWA and MWoA groups	The difference between the MWA and MWoA groups in the proportion of subjects reporting functional disability relief at 2 hours post-treatment in at least 50% of all their treatments. Functional disability relief is defined as an improvement of at least one grade from severe, moderate or mild disability from treatment initiation to 2 hours later.	2 hours
Comparison of Consistent Functional Disability Freedom at 2 Hours Post-treatment between the MWA and MWoA groups	The difference between the MWA and MWoA groups in the proportion of subjects reporting functional disability freedom at 2 hours post-treatment in at least 50% of all their treatments. Functional disability freedom is defined as the disappearance of disability from severe, moderate, or mild disability at treatment initiation to no disability 2 hours later.	2 hours
Comparison of Associated Symptoms Freedom at 2 Hours Post-treatment between the MWA and MWoA groups	The proportion of subjects reporting freedom from each of the migraine-associated symptoms (photophobia, phonophobia, nausea) in at least 50% of their treatments. Associated symptoms freedom is defined as reporting presence of a symptom at treatment initiation and reporting its absence 2 hours later.	2 hours
Device Related Adverse Events	Rate of serious adverse events, and device-related adverse events reported by subjects.	up to 30 months

Collaborators and Investigators

• Sponsor: Theranica
• Investigators: Principal Investigator: Alit Stark Inbar, PhD, Theranica Bio-Electronics ltd

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2023
• Primary Completion (Actual): September 30, 2024
• Study Completion (Actual): December 1, 2024

Study Registration Dates

• First Submitted: August 29, 2023
• First Submitted That Met QC Criteria: September 4, 2023
• First Posted (Actual): September 5, 2023

Study Record Updates

• Last Update Posted (Estimated): August 15, 2025
• Last Update Submitted That Met QC Criteria: August 11, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Migraine; Aura; REN; Nerivio
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Migraine with Aura; Epilepsy; Migraine without Aura
• Other Study ID Numbers: RWE006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No