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

Completed

• Conditions: Migraine With Aura; Migraine Without Aura

• Registration Number: NCT06023953
• Lead Sponsor: Theranica

Brief Summary

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.

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 Timeline

• Study Start: 2023-07-01
• Study First Submitted: 2023-08-29
• Study First Submitted QC: 2023-09-04
• Study First Posted: 2023-09-05
• Primary Completion: 2024-09-30
• Study Completion: 2024-12-01
• Status Verified: 2025-08
• Last Update Submitted: 2025-08-11
• Last Update Posted: 2025-08-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 31715

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Comparison of consistent Headache Relief at 2 Hours Post-treatment between the MWA and MWoA groups	2 hours	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.
Comparison of Headache Severity at treatment baseline (T=0h) between the MWA and MWoA groups	0 hours (at baseline)	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.

Secondary Outcome Measures

Name	Time	Method
Comparison of consistent Pain Freedom at 2 Hours Post-treatment between the MWA and MWoA groups	2 hours	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.
Comparison of Functional Disability at treatment baseline (T=0h) between the MWA and MWoA groups	0 hours (at baseline)	The difference between the MWA and MWoA groups in the proportion of subjects reporting severe/moderate disability in at least 50% of their attacks.
Comparison of Photophobia, Phonophobia and Nausea/vomiting presence at treatment baseline (T=0h) between the MWA and MWoA groups	0 hours (at baseline)	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.
Comparison of Consistent Functional Disability Relief at 2 Hours Post-treatment between the MWA and MWoA groups	2 hours	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.
Comparison of Consistent Functional Disability Freedom at 2 Hours Post-treatment between the MWA and MWoA groups	2 hours	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.
Comparison of Associated Symptoms Freedom at 2 Hours Post-treatment between the MWA and MWoA groups	2 hours	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.
Device Related Adverse Events	up to 30 months	Rate of serious adverse events, and device-related adverse events reported by subjects.

Trial Locations

Locations (1)

Theranica Bio-Electronics Ltd; 🇮🇱 Netanya, Israel