What is Nerivio?

Nerivio is a novel, remote electrical neuromodulation (REN) prescribed wearable that stimulates upper arm peripheral nerves to induce conditioned pain modulation (CPM) – an endogenous analgesic mechanism in which conditioning stimulation inhibits pain in remote body regions.

Migraine Pain Relief

How does Nerivio work?

Nerivio stimulates C and Aδ nociceptive sensory fibers of the upper arm above their depolarization thresholds but below the perceived pain threshold. The noxious information reaches the brainstem through the ascending pain pathway. This information activates the descending pain inhibitory pathway, involving the brainstem pain regulation center (which includes the PAG, RVM and subnucleus reticularis dorsalis [SRD]), and the release of serotonin and noradrenalin, which inhibit incoming messages of pain in the trigeminal cervical complex (TCC) that occur during a headache of a migraine attack.

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)

 

 

 

 

 

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.

 

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.

Publications

Publication

Nonpainful remote electrical stimulation alleviates episodic migraine pain

Objective: To evaluate the efficacy of remote nonpainful electrical upper arm skin stimulation in reducing migraine attack pain.
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Remote Electrical Neuromodulation (REN) Relieves Acute Migraine: A Randomized, Double‐Blind, Placebo‐Controlled, Multicenter Trial

Objective: To assess the efficacy and safety of a remote electrical neuromodulation (REN) device for the acute treatment of migraine.
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Remote electrical neuromodulation (REN) in the acute treatment of migraine: a comparison with usual care and acute migraine medications

There is a significant unmet need for new, effective and well tolerated acute migraine treatments.
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Remote Electrical Neuromodulation (REN) for the Acute Treatment of Migraine

There is a significant unmet need for new, effective and well tolerated acute migraine treatments.
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Device profile of the Nerivio for acute migraine treatment: overview of its efficacy and safety

There is a significant unmet need for new, effective and well tolerated acute migraine treatments.
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Incorporating Remote Electrical Neuromodulation (REN) Into Usual Care Reduces Acute Migraine Medication Use

This study investigated the clinical use of REN, focusing on its potential in reducing the use of acute migraine medications.
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Remote Electrical Neuromodulation for the Acute Treatment of Migraine in Patients with Chronic Migraine: An Open-Label Pilot Study

This was an open-label, single-arm, dual-center study conducted on adults with chronic migraine.
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Educational Material

What is Conditioned Pain Modulation?

Conditioned pain modulation (CPM) is a descending endogenous analgesic mechanism in which a nociceptive conditioning stimulus
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Favorable safety and efficacy profile

Nerivio is a novel remote neuromodulation device for the acute treatment of migraine.
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