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

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

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.

Study Overview

• Status: Completed
• Conditions: Migraine in Adolescence
• Intervention / Treatment: Device: Nerivio

Detailed Description

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:

1. - reduction in headache pain 2h post-treatment
2. - improve in functional disability
3. - A standalone treatment vs combination with other therapies
4. - 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.

• Study Type: Observational
• Enrollment (Actual): 1629

Contacts and Locations

Study Locations

• Israel
  • Netanya, Israel, 4250438
    • Theranica Bio-Electronics Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 18 years (ADULT, CHILD)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Adolescence (age 12-18) who suffers from migraine who are using the Nerivio device for acute treatment of migraine

Description

Inclusion Criteria:

1. - Age between 12-18 years
2. - REN user across the United States who created Nerivio account on January 1st, 2021 or later.
3. - Had at least two evaluable treatments with the Nerivio device

Exclusion Criteria:

(1) - Treatments shorter than 20 minutes

Study Plan

How is the study designed?

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment intensity distribution	The mean intensity of the stimulation collected for all treatments that were performed within the study	45 minutes post treatment
Device Related Adverse Events	Incidence of device-related adverse events reported by subjects	16 months

Collaborators and Investigators

• Sponsor: Theranica

Publications and helpful links

General Publications

• Yarnitsky D, Dodick DW, Grosberg BM, Burstein R, Ironi A, Harris D, Lin T, Silberstein SD. Remote Electrical Neuromodulation (REN) Relieves Acute Migraine: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial. Headache. 2019 Sep;59(8):1240-1252. doi: 10.1111/head.13551. Epub 2019 May 9.
• Nierenburg H, Rabany L, Lin T, Sharon R, Harris D, Ironi A, Wright P, Chuang L. Remote Electrical Neuromodulation (REN) for the Acute Treatment of Menstrual Migraine: a Retrospective Survey Study of Effectiveness and Tolerability. Pain Ther. 2021 Dec;10(2):1245-1253. doi: 10.1007/s40122-021-00276-7. Epub 2021 Jun 17.
• Grosberg B, Rabany L, Lin T, Harris D, Vizel M, Ironi A, O'Carroll CP, Schim J. Safety and efficacy of remote electrical neuromodulation for the acute treatment of chronic migraine: an open-label study. Pain Rep. 2021 Oct 14;6(4):e966. doi: 10.1097/PR9.0000000000000966. eCollection 2021 Nov-Dec.
• Hershey AD, Lin T, Gruper Y, Harris D, Ironi A, Berk T, Szperka CL, Berenson F. Remote electrical neuromodulation for acute treatment of migraine in adolescents. Headache. 2021 Feb;61(2):310-317. doi: 10.1111/head.14042. Epub 2020 Dec 21.
• Tepper SJ, Lin T, Montal T, Ironi A, Dougherty C. Real-world Experience with Remote Electrical Neuromodulation in the Acute Treatment of Migraine. Pain Med. 2020 Dec 25;21(12):3522-3529. doi: 10.1093/pm/pnaa299.
• Ailani J, Rabany L, Tamir S, Ironi A, Starling A. Real-World Analysis of Remote Electrical Neuromodulation (REN) for the Acute Treatment of Migraine. Front Pain Res (Lausanne). 2022 Jan 18;2:753736. doi: 10.3389/fpain.2021.753736. eCollection 2021.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 28, 2022
• Primary Completion (ACTUAL): August 15, 2022
• Study Completion (ACTUAL): August 24, 2022

Study Registration Dates

• First Submitted: June 25, 2022
• First Submitted That Met QC Criteria: June 29, 2022
• First Posted (ACTUAL): July 5, 2022

Study Record Updates

• Last Update Posted (ACTUAL): September 1, 2022
• Last Update Submitted That Met QC Criteria: August 29, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: migraine, Headache Nerivio, REN
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders
• Other Study ID Numbers: RWE003

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