Migraine Prevention With the Remote Electrical Neuromodulation (REN) Wearable: A Real-world Evidence Study

Preventive pharmacologic therapies for migraine aim to reduce attack frequency and duration and improve quality of life; however, their use, overall benefit and adherence are often limited, especially among patients with chronic migraine. Remote electrical neuromodulation (REN) is a non-invasive FDA-cleared wearable device for acute and/or preventive migraine treatment. This study evaluated the real-world efficacy and patient-reported outcomes of preventive REN use over 3 months in chronic migraine population.

Study Overview

• Status: Active, not recruiting
• Conditions: Migraine; Chronic Migraine Headache
• Intervention / Treatment: Device: Nerivio REN device

Detailed Description

Preventive treatment options for migraine aim to reduce attack frequency, severity, and duration, as well as the overall burden of disease, with the goal of improving patients' quality of life. The 2021 AHS Consensus Statement reports that preventive treatments are used by only 3%-13% of patients with migraine, despite potential benefits for almost 40% of all migraine patients and nearly all individuals with chronic migraine (CM). Existing pharmacological treatments include several classes, such as beta-adrenergic blockers, calcium channel blockers, antiepileptic agents, tricyclic antidepressants, and therapies targeting the calcitonin gene-related peptide (CGRP) pathway, including monoclonal antibodies and small-molecule antagonists. Different studies have demonstrated that these agents can reduce monthly migraine days (MMDs) and migraine-related disability. However, their clinical use is often limited due to adverse effects, reduced effectiveness, contraindications, high cost, and poor long-term adherence, resulting in high discontinuation rates in real-world practice. Analysis from a US database including more than 8,000 patients showed that over 80% of CM patients discontinue oral preventive therapy during the first year. These limitations highlight the need for effective, well-tolerated, and adherence-friendly preventive treatment alternatives.

Remote electrical neuromodulation (REN) is an FDA-cleared, non-invasive, non-pharmacologic prescribed wearable device indicated for the acute and/or preventive treatment of migraine in individuals aged 8 years and older. For acute treatment, REN is indicated for administration as early as possible at the onset of an attack to relieve pain and associated migraine symptoms. For preventive use, REN is indicated for treatment every other day to reduce migraine attack frequency.

The efficacy of REN for acute treatment of migraine attacks has been demonstrated in randomized controlled trials (RCTs), open-label studies, and many real-world evidence (RWE) studies. The efficacy of migraine prevention with the REN wearable has been also shown in an RCT. Preventive benefits were also shown in adolescents with high reduction in MMDs after 3 months of REN use. This study is the first to evaluate real-world preventive use of the REN wearable device in patients with CM, a population with high disease burden, assessing multiple efficacy and patient-reported outcomes following 3 months of treatment, in accordance with International Headache Society (IHS) guidelines.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Bridgewater, New Jersey, United States, 08807
      • Theranica Bio-Electronics Inc

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patient with migraine
• Prescribed with a Nerivio REN device
• Treat with nerivio in a preventive -like manner over 3 consecutive months from sign up.

Exclusion Criteria:

• NA

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Nerivio treatment; Nerivio users who were prescribed with the REN wearable for their routine migraine care and treated in a prevention-like manner over 3 consecutive months	Device: Nerivio REN device; 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-dministered and vcontrolled by a smartphone application

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in average number of monthly migraine days (MMD)	Change in average number of monthly migraine days (MMD) from baseline to 3-months follow-up questionnaire.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patients clinical improvement	Proportion of patients reporting improvement on PGIC scale at 3-months follow-up questionnaire.	3 months
Change in migraine attack duration	Change in average migraine attack duration from baseline to 3-months follow-up questionnaire.	3 months
Device Safety	Rate of serious adverse events, adverse events and device-related adverse events	3 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in acute migraine drug intake	Change in the percentage of treatments with acute migraine drug use.	3 months
Reduction of >30% in MMDs	A clinically meaningful response, defined as the percentage of patients achieving a ≥30% reduction in MMDs, migraine attack duration, and acute drug use. This threshold is recommended by the IHS for patients with CM	3 months

Collaborators and Investigators

• Sponsor: Theranica
• Investigators: Principal Investigator: Alit Stark Inbar, Theranica

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2026
• Primary Completion (Estimated): April 15, 2026
• Study Completion (Estimated): April 15, 2026

Study Registration Dates

• First Submitted: March 17, 2026
• First Submitted That Met QC Criteria: March 17, 2026
• First Posted (Actual): March 23, 2026

Study Record Updates

• Last Update Posted (Actual): March 23, 2026
• Last Update Submitted That Met QC Criteria: March 17, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Migraine prevention; REN; Nerivio
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders
• Other Study ID Numbers: RWE-012

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