Dr. Blumenfeld, neurologist, explains the science behind Nerivio

How Does Nerivio Work?

A 2019 study published in the clinical journal Headache showed that Nerivio lessened migraine symptoms within two hours for most participants, and completely alleviated head pain for over a third

See clinical data

66.7% of
patients

achieve pain relief at 2 hours
(Yarnitsky et al., Headache)

Non-invasive
Non-addictive
Non-pharmacological

Smart &
Personalized

From the arm to the brain

Nerivio stimulates small nerves in the upper arm. The message from the arm is received by a brainstem pain regulation center that can inhibit pain signals by releasing neurotransmitters, resulting in significant pain relief which can end the migraine attack.

Nerivio Method of operation illustration
mechanism of operation illustration mobile

Clinical Data

Nerivio was evaluated in two clinical studies. The first study was a prospective, double-blind, randomized, crossover, sham-controlled pilot study and the second study was a multi-center, prospective, randomized, double-blind, sham-controlled pivotal study.

Pilot Study

The results of the pilot study were published in Neurology, March 2017:
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The pilot study was a single-center, prospective, double-blind, randomized, crossover, sham-controlled pilot study aimed to assess the safety and efficacy of non-invasive remote electrical neuromodulation (REN) with the Nerivio device for the acute treatment of migraine. In this study, 86 people with migraine with or without aura (in accordance with International Classification of Headache Disorders [ICHD] classification criteria) who had 2–8 attacks per month without preventive medications for at least 2 months were recruited. The participants were requested to treat migraine episodes at home using the device, which randomly provided one of four different stimuli programs differentiating in pulse width and one sham stimulus. Pain levels were self-reported via…

Pivotal Study

The results of the pivotal study were published in Headache, May 2019:
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The pivotal study (TCH-003) was a prospective, randomized, double-blind, sham controlled multi-center study aimed to demonstrate the safety and efficacy of the Nerivio remote electrical neuromodulation device for the acute treatment of migraine with or without aura. This study was conducted from December 2017 to October 2018 at 12 sites, 7 in the US and 5 in Israel.

296 participants with migraine with or without aura (in accordance with ICHD classification criteria) who had 2–8 attacks per month, ≤12 headache days per month, and were on either no or stable migraine preventive medications in the last two months prior to recruitment were enrolled. 252 participants were randomized to active (n=126) or sham stimulation (n=126). Headache pain levels were reported at baseline, 2 hours and 48 hours post-treatment. The primary efficacy endpoint of the study was the percentage of participants reporting reduction in their pain level, without use of medication, from severe or moderate to mild or no pain or from mild to no pain within 2 hours.  Sustained pain relief or pain-free status was defined as having a headache response at 2 hours post-treatment with no use of rescue medication and no return to baseline or relapse of headache pain within 48 hours.  The analyses were performed on 202 participants (99 in the active group and 103 in the sham group) who treated an attack within one hour from symptoms onset and reported pain level at 2 hours post-treatment. At 2 hours post-treatment, active stimulation was significantly more effective than sham stimulation in reducing headache pain (66.7% vs. 38.8%, p<0.0001)), in completely relieving headaches (37.4% vs 18.4%, p=0.005), in reducing the most bothersome symptom (MBS) of the associated symptoms of nausea, sensitivity to light and sensitivity to sound (46.3%% vs. 22.2%, p=0.001) and in reducing the combination of headache and MBS (40.0% vs. 15.2%, p<0.001). The 2-hours pain relief and pain-free superiority of the active treatment were sustained 48 hours post-treatment; sustained pain relief at 48 hours post-treatment was achieved by 39.1% of the participants in the active group versus 16.9% in the sham group (p<0.005) and sustained pain free status at 48 hours post-treatment was achieved by 20.7% of the participants in the active group versus 7.9% in the sham group (p<0.005)

 

response at 2 hours post-treatment graphresponse at 2 hours post-treatment graph mobile

 

 

 

sustained response at 48 hours post-treatment graphsustained response at 48 hours post-treatment graph mobile

 

Moreover, pain relief at 2 hours post-treatment was consistent across multiple treatments (62.6% of the participants in the active group achieved pain relief in at least 50% of their attacks vs. 45.6% in the sham group, p<0.05).

This study also demonstrated a favorable safety profile for Nerivio. The incidence of device-related adverse events was low (3.6% of participants) and the event rate was similar between the active (Nerivio) and sham treatment groups. During 773 treatments, 23 (2.7%) device-related adverse events were reported, 14 in the active group and 9 in the sham group. All device-related adverse events were mild, did not require treatment and resolved within 24 hours. No device-related serious adverse events were reported and none of the participants withdrew from the study due to adverse events.

 

device-related adverse events graphdevice-related adverse events graph

In conclusion, the results of the pivotal study indicate that Nerivio is safe and effective for the acute treatment of migraine. The findings of this study were robust and clinically meaningful. Nerivio, thus, offers a novel alternative for current pharmacological and non-pharmacological treatments that combines effective treatment with minimal side effects.

Pilot study with chronic migraine patients

The results of the pilot study were published in Pain and Therapy, July 2020
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The pilot study (TCH-005) was prospective, open-label, single arm, dual-center study aimed to demonstrate the safety and efficacy of Nerivio remote electrical neuromodulation device for the acute treatment of migraine with or without aura in patients with chronic migraine (>15 headache days/month). This study was conducted from September 2019 to February 2020 at 2 sites (USA -1, Israel – 1). 42 participants were enrolled, and 38 participants were evaluable for analyses. A total of 210 evaluable treatments (excluding the training treatment) of qualifying migraine headaches were conducted by the 38 participants included in the analyses, with an average of 5.5±2.6 evaluable treatments per patient per 4 weeks.…

Main study with chronic migraine patients

The results of the main study will be published in Pain Reports, November 2021
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The main study (TCH-006) was prospective, open-label, single arm, multi-center study aimed to demonstrate the safety and efficacy of Nerivio remote electrical neuromodulation device for the acute treatment of migraine with or without aura in patients with chronic migraine (>15 headache days/month). This study was conducted from November 2019 to June 2020 at 9 sites in the USA. Participants entered a 4-week “Run-in” phase in which they had to report their migraine attacks and continue with their usual treatment care. Participants who reported at least 6 qualifying migraine headaches with pain data at baseline and 2 hours post-treatment were eligible to continue to the “Treatment” phase Run-in…

Study with Adolescent Migraine Patients

The results of the pivotal study were published in Headache, December 2020
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The study was a prospective, open-label, single arm, multicenter study of the Nerivio device in adolescent patients (age 12-17, inclusive), aiming to assess the performance of Nerivio in the adolescent migraine population. study was conducted from October 2019 to May 2020 (Clinicaltrials.gov number – NCT04089761). Study design and procedures Eligible participants were enrolled based on the inclusions/exclusions criteria. Following enrollment, participants entered a 4-week “Run-in” phase in which they had to report their migraine attacks and continue with their usual treatment care. Participants who reported at least 3 qualifying migraine headaches with pain data at baseline and 2 hours post-treatment were eligible to continue to the “Treatment”…

Post Hoc Analysis

The results of the post-hoc analysis were published in Pain medicine, June 2021
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In addition, a post hoc analysis (TCH-004) of comparison between the Nerivio treatment (REN) and Standard-Care Medications for Acute Treatment of Migraine was performed. Four efficacy endpoints were tested: pain freedom and pain relief (severe to mild or no pain, or moderate to no pain—two-step improvement) after a single treatment, and pain freedom and pain relief consistency across treatments. All endpoints refer to 2 hours after treatment. For the single-treatment endpoints. The analyzed test treatment for REN was defined as the first REN treatment after a training treatment, and the test treatment for medications was defined as the first treatment in the run-in phase in which medication…

Retrospective Study with Menstrual Migraine Patients

The results of the study were published in Pain and Therapy, June 17, 2021
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The Retrospective Survey Study (TCH-009) evaluated the self-reported effectiveness and tolerability of the Nerivio device for the acute treatment of menstrual migraine, via a retrospective structured survey that was sent to adult female Nerivio users. Women aged 18–55 years who experience menstrually related or pure menstrual migraine and have completed at least four Remote Electrical Neuromodulation (REN) treatments with the Nerivio device, participated in this retrospective, observational survey study. Participants completed a short online survey assessing effectiveness, satisfaction, and safety outcomes. The survey was sent to 455 female patients aged 18–55 across the United States who used Nerivio between October 1, 2019, and October 18, 2020, and…