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Migraine in AdolescenceNCT05443659

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

An observational study of Migraine in Adolescence, run by Theranica at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 12 to 18 years
Conditions the study is for
Migraine in Adolescence
What is being tested?
Nerivio
Type of treatment
Medical device
How many people
1,629 participants
Where
2 sitesin 2 countries
Study dates
1 Jan 2021to 24 Aug 2022
Phase
Observational
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 to 18 years
  • All sexes
  • Child, Adult

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

Who may be able to join

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

Who cannot join

  • - Treatments shorter than 20 minutes

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

United States1 site

  • Theranica USA Inc

    Bridgewater, New Jersey, 08807

Other trials in United States

Israel1 site

  • Theranica Bio-Electronics Ltd

    Netanya, 4250438

Other trials in Israel

About this study

Official title: 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.

Read the 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.

Being tested
Nerivio
Keywords
migraine, Headache Nerivio, REN
Medical subject headings
Migraine Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NerivioDevice

    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.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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)

    Measured: 2 hours post treatment, up to 16 months from the 1st treatment

Secondary outcomes (4)

  1. 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)

    Measured: 2 hours post treatment, up to 16 months from the 1st treatment

  2. 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), or with a combination of rescue medication or without any treatment at all at 2 hours post-treatment in at least 50% of all their treatments.

    Measured: 2 hours post treatment, up to 16 months from the 1st treatment

  3. 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)

    Measured: 2 hours post treatment, up to 16 months from the 1st treatment

  4. 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).

    Measured: 2 hours post treatment, up to 16 months from the 1st treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Jul 2022
  2. Study start1 Jan 2021
  3. Primary completion31 May 2022
  4. Study completion24 Aug 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
1,629 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05443659
Sponsor's protocol ID
RWE003
Status last verified
Aug 2025
First submitted
25 Jun 2022
Last updated
4 Nov 2025
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
Yes
Individual data sharing
No

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.

    PubMed 31074005

  • 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.

    PubMed 34138449

  • 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.

    PubMed 34667919

  • 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.

    PubMed 33349920

  • 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.

    PubMed 32935848

  • Esparham A, Stark-Inbar A, Jekel L, Tamir S, Rabany L, Ironi A, Gautreaux J, Rao R. Acute Treatment of Migraine in Adolescents: Real-World Analysis of Remote Electrical Neuromodulation (REN). Pediatr Neurol. 2023 May;142:51-55. doi: 10.1016/j.pediatrneurol.2023.02.008. Epub 2023 Feb 21.

    PubMed 36931109

  • 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.

    PubMed 35295483

Questions about this trial

What is this clinical trial studying?

An observational study of Migraine in Adolescence, run by Theranica at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States, Israel. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Nov 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Consistent Pain Relief at 2 Hours Post-treatment (time frame: 2 hours post treatment, up to 16 months from the 1st treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05443659, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2025.

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