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

• ClinicalTrials.gov Identifier: NCT05443659
• Recruitment Status: Completed
• First Posted: July 5, 2022
• Last Update Posted: September 1, 2022
• Sponsor: Theranica
• Information provided by (Responsible Party): Theranica

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment
Migraine in Adolescence	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 Design

• Study Type: Observational
• Actual Enrollment: 1629 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Real-World Analysis of Remote Electrical Neuromodulation (REN) for the Acute Treatment of Migraine in Adolescence
• Actual Study Start Date: July 28, 2022
• Actual Primary Completion Date: August 15, 2022
• Actual Study Completion Date: August 24, 2022

Groups and Cohorts

Intervention Details:

• Device: Nerivio
  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-administered and controlled by a smartphone application.

Outcome Measures

Primary Outcome Measures :

1. Consistent Pain Relief at 2 Hours Post-treatment [ Time Frame: 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)

Secondary Outcome Measures :

1. Consistent Pain Freedom at 2 Hours Post-treatment [ Time Frame: 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. Consistent Usage of Migraine Abortive (Rescue) Medications [ Time Frame: 2 hours post treatment ]
   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.
3. Consistent Functional Disability Relief at 2 Hours Post-treatment [ Time Frame: 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)
4. Consistent Functional Disability disappearance at 2 Hours Post-treatment [ Time Frame: 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).

Other Outcome Measures:

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

Eligibility Criteria

• Ages Eligible for Study: 12 Years to 18 Years (Child, Adult)
• Sexes 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

Criteria

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

Contacts and Locations

Locations

Israel

Theranica Bio-Electronics Ltd

Netanya, Israel, 4250438

Sponsors and Collaborators

Theranica

Investigators

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

More Information

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.

• Responsible Party: Theranica
• ClinicalTrials.gov Identifier: NCT05443659
• Other Study ID Numbers: RWE003
• First Posted: July 5, 2022
• Last Update Posted: September 1, 2022
• Last Verified: June 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Theranica:

migraine, Headache Nerivio, REN

Additional relevant MeSH terms:

Migraine Disorders; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases