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

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

This is a Post-marketing 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. 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 smartphone application that is downloaded to the user's phone prior first use of the Nerivio device.

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.

Post-marketing surveillance is designed to assess the safety and efficacy of REN in larger and more diverse populations than in clinical trials 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.

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. - Safety - all adverse events that were reported during the study's period
2. - Efficacy - pain relief, freedom from pain, improvement in functional disability, and return to normal function (no disability) at 2 hours post-treatment 3 - Disease severity -severe headache pain, presence of associated symptoms.

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): 24446

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:

• Age 12 years old and above
• REN users across the USA who created Nerivio accounts between October 2019 and February 2023.
• Treated acute migraine at least once with Nerivio device
• Reported at least one treatment questionnaire at T=0h and T=2h

Exclusion Criteria:

• Treatments shorter than 30 minutes

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 used the Nerivio device at least once and reported having aura in at least one treatment	Device: Nerivio device; REN treatment with Nerivio device
Migraine without aura (MWoA ); Patients with migraine who used the Nerivio device at least once and never reported having aura in any of their treatments	Device: Nerivio device; REN treatment with Nerivio device

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Consistent Headache Relief at 2 Hours Post-treatment	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
Device Related Adverse Events	Incidence of device-related adverse events reported by subjects	40 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Consistent Freedom From Headache at 2 Hours Post-treatment	The proportion of subjects reporting freedom from headache at 2 hours post-treatment in at least 50% of all their treatments. Pain freedom is defined as the disappearance of headache from severe, moderate, or mild headache at treatment initiation to no headache 2 hours later	2 hours
Severe Headache Pain during migraine attack	The proportion of subjects reporting severe headache pain in at least 50% of their attacks.	2 hours
Associated Symptoms Relief	The proportion of subjects reporting each of the migraine-associated symptoms (photophobia, phonophobia, nausea) in at least 50% of their attacks.	2 hours

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): July 30, 2023
• Study Completion (Actual): August 1, 2023

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 (Actual): December 22, 2023
• Last Update Submitted That Met QC Criteria: December 16, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: migraine; REN; Nerivio
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Epilepsy; Migraine Disorders; Migraine without Aura; Migraine with 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: Yes
• product manufactured in and exported from the U.S.: No