MigraineNCT04992897
Real-world Data Analysis of REN Treatment in Migraine Patients
An observational study of Migraine, run by Theranica at 2 sites in 2 countries.
Trial summary
Data analysis concerning four sets of metrics: A. Per-treatment patterns of REN use as a standalone treatment vs. in combination with medications. B. Per-user Intra-individual consistency of efficacy across multiple treatments (consistency defined as a response to treatment in at least 50% of treatments). C. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Migraine
- What is being tested?
- Remote Electrical Neuromodulation (REN)
- Type of treatment
- Medical device
- How many people
- 12,151 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 15 Jun 2021to 10 Aug 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: REN users across the United States who used Nerivio between October 1st, 2019, and May 24th, 2021.
Who may be able to join
- REN users in the U.S.
Who cannot join
- Cohort 1 REN treatments that were shorter than 20 minutes or did not have a report of pain level.
- Cohort 2 Treatments in which medications were taken within 2 hours from REN treatment. Users that had less than 2 REN treatments.
- Cohort 3 REN treatments that were shorter than 20 minutes
- Cohort 4 All REN sessions, regardless of duration or medication intake.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: Real-world Analysis of Remote Electrical Neuromodulation (REN) for the Acute Treatment of Migraine
Data analysis concerning four sets of metrics: A. Per-treatment patterns of REN use as a standalone treatment vs. in combination with medications. B. Per-user Intra-individual consistency of efficacy across multiple treatments (consistency defined as a response to treatment in at least 50% of treatments). C. Distribution of treatment intensity among users (the electroceutical equivalent to treatment dose). D. Prevalence and severity of adverse events.
Read the detailed description
The REN device The REN device is a wearable device applied to the upper arm and 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 can be adjusted by the patient.
Data collection 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 were 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 indication of which medications, if any, were taken within that 2-hour time window.
Dataset Real-world data of REN treatments collected from patients across the United States who used the REN device.
'Treatment' defined as a REN treatment of at least 20 minutes (the nominal duration is 45 minutes).
'Evaluable treatment' defined as a treatment in which pain levels were reported at baseline and post 2 hours.
Inclusion criteria for each of the different metrics:
- REN-medication combinations: all evaluable treatments. B. Consistent efficacy: all users that performed at least 2 evaluable treatments. In order to isolate the effect of REN treatments, this dataset considered only treatments where REN was used as a standalone treatment.
- Intensity stability: all treatments. D. Safety: all reported adverse events (AEs) within the time period.
Outcome measures
Respectively, outcome measures:
- REN-Medication combinations (prevalence \& efficacy):
Medication intake outcomes calculated based on the 2h post-treatment report and comprised of the percentage of treatments in which no rescue medications were used, treatments in which OTC medications were taken, treatments in which triptans were taken, treatments in which other prescription medications were taken, and treatments in which medication intake status was not reported. OTC included acetaminophen, NSAIDs, and combinations of the two, with or without caffeine.
Efficacy outcomes calculated based on the baseline and post-2h reports and comprised of:
(i) consistency of pain relief (decrease in headache from moderate or severe at baseline to mild or no pain); (ii) consistency of pain-freedom (decrease in headache from mild, moderate, or severe at baseline to no pain); (iii) Consistency of improvement in function (improvement in at least one grade between baseline and 2 hours); and (iv) consistency of return to normal function (no functional disability at 2 hours).
- Consistent efficacy:
Consistency defined as a response of a patient to the treatment in at least 50% of their treated attacks, and calculated for the four efficacy outcomes: (i) consistency of pain relief (ii) consistency of pain-freedom (iii) consistency of improvement in function; and (iv) consistency of return to normal function.
- Treatment intensity:
The mean intensity of the stimulation collected for all treatments that were 20 minutes or longer, which were performed within the study's time window.
- Safety:
All adverse events that were reported within the study's period, the following information provided: number of device-related AEs, percentage of the device-related AEs that were mild, moderate, and severe, and percentage of AEs that were serious vs. not serious.
- Conditions
- Migraine
- Being tested
- Remote Electrical Neuromodulation (REN)
- Keywords
- Migraine, headache, REN, Nerivio
- Medical subject headings
- Migraine Disorders, Headache
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Remote Electrical Neuromodulation (REN)Device
Also called Nerivio
Acute migraine treament
| Study group | Role | What they receive |
|---|---|---|
| REN-Medication combinations | all evaluable treatments.
'Treatment' defined as a REN treatment of at least 20 minutes (the nominal duration is 45 minutes).
'Evaluable treatment' defined as a treatment in which pain levels were reported at baseline and post 2 hours. Receives: Device: Remote Electrical Neuromodulation (REN) | |
| Consistent efficacy | all users that performed at least 2 evaluable treatments. In order to isolate the effect of REN treatments, this dataset considered only treatments where REN was used as a standalone treatment.
'Treatment' defined as a REN treatment of at least 20 minutes (the nominal duration is 45 minutes).
'Evaluable treatment' defined as a treatment in which pain levels were reported at baseline and post 2 hours. Receives: Device: Remote Electrical Neuromodulation (REN) | |
| Treatment intensity distribution | all treatments.
'Treatment' defined as a REN treatment of at least 20 minutes (the nominal duration is 45 minutes). Receives: Device: Remote Electrical Neuromodulation (REN) | |
| Safety | all reported treatment/device-related adverse events (AEs) within the time period. Receives: Device: Remote Electrical Neuromodulation (REN) |
What is being measured
The primary outcome is the main question the study is designed to answer.
REN-medication combinations- prevalence
Medication intake outcomes calculated based on the 2h post-treatment report and comprised of the percentage of treatments in which no rescue medications were used, treatments in which OTC medications were taken, treatments in which triptans were taken, treatments in which other prescription medications were taken, and treatments in which medication intake status was not reported. OTC included acetaminophen, NSAIDs, and combinations of the two, with or without caffeine.
Measured: 2 hours from treatment onset
REN-medication combinations- efficacy of the combinations
The efficacy of treatments in which medications were taken will be calculated based on the 2 hours post-treatment pain report. The overall efficacy rate will be calculated as the percentage of treatments in which response to the treatment was achieved, out of all the treatments.
Measured: 2 hours from treatment onset
percentage of users that achieve consistency of efficacy
Consistency defined as a response of a patient to the treatment in at least 50% of their treated attacks, and calculated for the four efficacy outcomes: (i) consistency of pain relief (ii) consistency of pain-freedom (iii) consistency of improvement in function; and (iv) consistency of return to normal function.
Measured: 2 hours from treatment onset
Treatment intensity distribution
The mean intensity of the stimulation collected for all treatments that were 20 minutes or longer, which were performed within the study's time window.
Measured: 20 minutes from treatment onset
Safety (number of users reporting device/treatment-related adverse events)
The percentage of users reporting adverse events, out of the overall number of users, and the severity of the treatment/device-related adverse events.
Measured: 20 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2021
- Study start15 Jun 2021
- Primary completion7 Aug 2021
- Study completion10 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for MigraineStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Retrospective
- Enrolment
- 12,151 participants (actual)
Sponsor and investigators
- Lead sponsor
- Theranica
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Georgetown University, Mayo Clinic
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04992897
- Sponsor's protocol ID
- RW002
- Status last verified
- Jul 2021
- First submitted
- 4 Jul 2021
- Last updated
- 22 Nov 2024
- Results posted
- No
- 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 31074005Tepper 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 32935848Hershey 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 33349920Nierenburg H, Vieira JR, Lev N, Lin T, Harris D, Vizel M, Ironi A, Lewis B, Wright P. Remote Electrical Neuromodulation for the Acute Treatment of Migraine in Patients with Chronic Migraine: An Open-Label Pilot Study. Pain Ther. 2020 Dec;9(2):531-543. doi: 10.1007/s40122-020-00185-1. Epub 2020 Jul 9.
PubMed 32648205Rapoport AM, Lin T. Device profile of the Nerivio for acute migraine treatment: overview of its efficacy and safety. Expert Rev Med Devices. 2019 Dec;16(12):1017-1023. doi: 10.1080/17434440.2019.1695599. Epub 2019 Nov 25.
PubMed 31747304Marmura MJ, Lin T, Harris D, Ironi A, Rosen NL. Incorporating Remote Electrical Neuromodulation (REN) Into Usual Care Reduces Acute Migraine Medication Use: An Open-Label Extension Study. Front Neurol. 2020 Apr 7;11:226. doi: 10.3389/fneur.2020.00226. eCollection 2020.
PubMed 32318014
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Real-world Analysis of Remote Electrical Neuromodulation (REN) for the Acute Treatment of Migraine
- ClinicalTrials.gov ID
- NCT04992897
- Acronym / sponsor ID
- RW002
- Conditions
- Migraine
- Keywords
- Migraine, headache, REN, Nerivio
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 12,151 participants (actual)
- Lead sponsor
- TheranicaIndustry (pharma, biotech, devices)
- Collaborators
- Georgetown University, Mayo Clinic
- Study start
- 15 Jun 2021 (actual)
- Primary completion
- 7 Aug 2021 (actual)
- Study completion
- 10 Aug 2021 (actual)
- First posted
- 5 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Data analysis concerning four sets of metrics: A. Per-treatment patterns of REN use as a standalone treatment vs. in combination with medications. B. Per-user Intra-individual consistency of efficacy across multiple treatments (consistency defined as a response to treatment in at least 50% of treatments). C. Distribution of treatment intensity among users (the electroceutical equivalent to treatment dose). D. Prevalence and severity of adverse events.
Detailed description
The REN device The REN device is a wearable device applied to the upper arm and 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 can be adjusted by the patient.
Data collection 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 were 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 indication of which medications, if any, were taken within that 2-hour time window.
Dataset Real-world data of REN treatments collected from patients across the United States who used the REN device.
'Treatment' defined as a REN treatment of at least 20 minutes (the nominal duration is 45 minutes).
'Evaluable treatment' defined as a treatment in which pain levels were reported at baseline and post 2 hours.
Inclusion criteria for each of the different metrics:
- REN-medication combinations: all evaluable treatments. B. Consistent efficacy: all users that performed at least 2 evaluable treatments. In order to isolate the effect of REN treatments, this dataset considered only treatments where REN was used as a standalone treatment.
- Intensity stability: all treatments. D. Safety: all reported adverse events (AEs) within the time period.
Outcome measures
Respectively, outcome measures:
- REN-Medication combinations (prevalence \& efficacy):
Medication intake outcomes calculated based on the 2h post-treatment report and comprised of the percentage of treatments in which no rescue medications were used, treatments in which OTC medications were taken, treatments in which triptans were taken, treatments in which other prescription medications were taken, and treatments in which medication intake status was not reported. OTC included acetaminophen, NSAIDs, and combinations of the two, with or without caffeine.
Efficacy outcomes calculated based on the baseline and post-2h reports and comprised of:
(i) consistency of pain relief (decrease in headache from moderate or severe at baseline to mild or no pain); (ii) consistency of pain-freedom (decrease in headache from mild, moderate, or severe at baseline to no pain); (iii) Consistency of improvement in function (improvement in at least one grade between baseline and 2 hours); and (iv) consistency of return to normal function (no functional disability at 2 hours).
- Consistent efficacy:
Consistency defined as a response of a patient to the treatment in at least 50% of their treated attacks, and calculated for the four efficacy outcomes: (i) consistency of pain relief (ii) consistency of pain-freedom (iii) consistency of improvement in function; and (iv) consistency of return to normal function.
- Treatment intensity:
The mean intensity of the stimulation collected for all treatments that were 20 minutes or longer, which were performed within the study's time window.
- Safety:
All adverse events that were reported within the study's period, the following information provided: number of device-related AEs, percentage of the device-related AEs that were mild, moderate, and severe, and percentage of AEs that were serious vs. not serious.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| REN-Medication combinations | – | Device: Remote Electrical Neuromodulation (REN)all evaluable treatments. 'Treatment' defined as a REN treatment of at least 20 minutes (the nominal duration is 45 minutes). 'Evaluable treatment' defined as a treatment in which pain levels were reported at baseline and post 2 hours. |
| Consistent efficacy | – | Device: Remote Electrical Neuromodulation (REN)all users that performed at least 2 evaluable treatments. In order to isolate the effect of REN treatments, this dataset considered only treatments where REN was used as a standalone treatment. 'Treatment' defined as a REN treatment of at least 20 minutes (the nominal duration is 45 minutes). 'Evaluable treatment' defined as a treatment in which pain levels were reported at baseline and post 2 hours. |
| Treatment intensity distribution | – | Device: Remote Electrical Neuromodulation (REN)all treatments. 'Treatment' defined as a REN treatment of at least 20 minutes (the nominal duration is 45 minutes). |
| Safety | – | Device: Remote Electrical Neuromodulation (REN)all reported treatment/device-related adverse events (AEs) within the time period. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- REN users across the United States who used Nerivio between October 1st, 2019, and May 24th, 2021.
Key inclusion criteria (1 listed)
- REN users in the U.S.
Key exclusion criteria (4 listed)
- Cohort 1 REN treatments that were shorter than 20 minutes or did not have a report of pain level.
- Cohort 2 Treatments in which medications were taken within 2 hours from REN treatment. Users that had less than 2 REN treatments.
- Cohort 3 REN treatments that were shorter than 20 minutes
- Cohort 4 All REN sessions, regardless of duration or medication intake.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Remote Electrical Neuromodulation (REN)Also: NerivioAcute migraine treament | Device | Consistent efficacy, REN-Medication combinations, Safety, Treatment intensity distribution |
Primary outcome
REN-medication combinations- prevalence
Time frame: 2 hours from treatment onset
Medication intake outcomes calculated based on the 2h post-treatment report and comprised of the percentage of treatments in which no rescue medications were used, treatments in which OTC medications were taken, treatments in which triptans were taken, treatments in which other prescription medications were taken, and treatments in which medication intake status was not reported. OTC included acetaminophen, NSAIDs, and combinations of the two, with or without caffeine.
REN-medication combinations- efficacy of the combinations
Time frame: 2 hours from treatment onset
The efficacy of treatments in which medications were taken will be calculated based on the 2 hours post-treatment pain report. The overall efficacy rate will be calculated as the percentage of treatments in which response to the treatment was achieved, out of all the treatments.
percentage of users that achieve consistency of efficacy
Time frame: 2 hours from treatment onset
Consistency defined as a response of a patient to the treatment in at least 50% of their treated attacks, and calculated for the four efficacy outcomes: (i) consistency of pain relief (ii) consistency of pain-freedom (iii) consistency of improvement in function; and (iv) consistency of return to normal function.
Treatment intensity distribution
Time frame: 20 minutes from treatment onset
The mean intensity of the stimulation collected for all treatments that were 20 minutes or longer, which were performed within the study's time window.
Safety (number of users reporting device/treatment-related adverse events)
Time frame: 20 months
The percentage of users reporting adverse events, out of the overall number of users, and the severity of the treatment/device-related adverse events.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2024.
- Background: PubMed 31074005Yarnitsky 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.
- Background: PubMed 32935848Tepper 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.
- Background: PubMed 33349920Hershey 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.
- Background: PubMed 32648205Nierenburg H, Vieira JR, Lev N, Lin T, Harris D, Vizel M, Ironi A, Lewis B, Wright P. Remote Electrical Neuromodulation for the Acute Treatment of Migraine in Patients with Chronic Migraine: An Open-Label Pilot Study. Pain Ther. 2020 Dec;9(2):531-543. doi: 10.1007/s40122-020-00185-1. Epub 2020 Jul 9.
- Background: PubMed 31747304Rapoport AM, Lin T. Device profile of the Nerivio for acute migraine treatment: overview of its efficacy and safety. Expert Rev Med Devices. 2019 Dec;16(12):1017-1023. doi: 10.1080/17434440.2019.1695599. Epub 2019 Nov 25.
- Background: PubMed 32318014Marmura MJ, Lin T, Harris D, Ironi A, Rosen NL. Incorporating Remote Electrical Neuromodulation (REN) Into Usual Care Reduces Acute Migraine Medication Use: An Open-Label Extension Study. Front Neurol. 2020 Apr 7;11:226. doi: 10.3389/fneur.2020.00226. eCollection 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Migraine, 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 1 inclusion and 4 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 22 Nov 2024. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
REN-medication combinations- prevalence (time frame: 2 hours from treatment onset). The study lists 5 primary outcomes in all. 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 NCT04992897, which also lists 6 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 22 Nov 2024.