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External Vagus Nerve Stimulator for Episodic Cluster Headaches Is Coming to the US Market Soon

ARTICLE IN BRIEF

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THE NONINVASIVE DEVICE was approved for episodic cluster headache by the Food and Drug Administration in April.

A noninvasive device designed to stimulate the vagus nerve holds promise for treating cluster headaches, migraine experts said.

A small hand-held device designed to stimulate the vagus nerve has a potential place in the lineup of treatments for episodic cluster headache, migraine experts told Neurology Today.

The device, called gammaCore, was cleared for marketing in April by the United States Food and Drug Administration (FDA) and is expected to be available by prescription in the US by fall. The stimulator is about the size of a cell phone and is applied to the neck when an attack comes on.

Two randomized, controlled trials that compared the vagus nerve stimulator to a sham device found that between 34 percent and 48 percent of patients with episodic cluster headache who used the stimulator achieved pain relief compared to about 6 percent to 10 percent of those in the sham group. The studies did not find a benefit for patients with chronic cluster headache.

There are also some hints from ongoing research that the device may help prevent cluster headache, though that hasn't been proven.

The device, which is marketed by electroCore, a New Jersey company, is already available in Europe, and clinicians in the United States say that headache patients are asking for it.

“Cluster headaches are sometimes called suicide headaches because they are very debilitating,” said Alexander Mauskop, MD, FAAN, director of the New York Headache Center and professor of clinical neurology at the State University of New York, Downstate Medical Center. He said cluster headaches are difficult to manage, and acute treatments, including injectable sumatriptan and inhaled oxygen, do not always help. Some people experience multiple attacks a day.

“It is always good to have another option to try even if it only works 30 to 40 percent of the time,” said Dr. Mauskop, who participated in a study of gammaCore for acute migraine.

He also did a study more than a decade ago in which six patients with either refractory migraine or refractory cluster headache were treated with an implanted vagus nerve stimulator.

Dr. Mauskop said the device is easy to use and appears to be safe, according to published results.

Cluster headache is a less common type of headache, occurring in about one to two of every one thousand people. Most people's cluster headaches come and go, sometimes with months or even years between attacks, while a minority of people have a chronic form of the condition.

“Cluster headache is in desperate need of new treatments,” said Matthew S. Robbins, MD, FAAN, associate professor of clinical neurology at Albert Einstein College of Medicine and chief of neurology at Jack D. Weiler Hospital, Montefiore Medical Center. He said sumatriptan “works great for most people, but there are quantity limits that insurance companies place on it.” For someone who gets multiple cluster headaches a day, the repeated need for injections is problematic, he said.

High-flow oxygen, another treatment, also has limited insurance coverage, doesn't help in all instances, and is cumbersome to tote about.

The vagus nerve stimulator “is a logistically and easier treatment modality because it's this tiny hand-held device that doesn't hurt and is easily tolerated,” said Dr. Robbins. The exact mechanism by which stimulation of the vagus nerve relieves headache pain is not fully understood, though Dr. Robbins said there are “connections between vagus nerve afferents and the trigeminal nociceptive system.”

The first major study on gammaCore for cluster headache, called the ACT1 trial, was published last September in Headache. It included 60 patients who were randomly assigned to use the vagus nerve stimulator when an attack began and 73 who used a sham device. The primary endpoint was the proportion of participants who achieved pain relief (0 or 1 on a five-point scale) within 15 minutes after the attack began and without the use of rescue medicine for 60 minutes.

The difference in response rate between the two groups was not statistically significant, but when the researchers analyzed subgroups, those with episodic cluster headache and those with chronic cluster headache, they found an advantage for the episodic patients. Of those who used the vagus nerve stimulator 34.2 percent experienced pain relief compared to 10.6 percent who used the sham device.

EUROPEAN STUDY

A similar pattern emerged in a second trial, called ACT2. An abstract of the results was presented at the AAN Annual Meeting in April in Boston. The study, done in Europe and funded by electroCore, likewise found that the stimulator helped persons with episodic cluster headache compared to the control group (48 percent versus 6 percent), but it didn't make a difference for chronic cluster headache.

Lead investigator Peter Goadsby, MD, PhD, professor of neurology at King's College London and professor of neurology at University of California, San Francisco (UCSF), said the results from the two clinical trials combined with clinical experience with the device in Europe make “it quite clear that there are patients with cluster headache who do very well with the device.”

Dr. Goadsby said that while the response rate was less than half, “nothing works in everybody.” He said the device may be particularly appealing to patients because it can be used multiple times in a day, works quickly, and seems safe.

“Speed of onset is important to patients,” Dr. Goadsby said. He said experience with the device in Europe is suggesting that after a couple of months “it actually starts to have a preventive effect.”

Morris Levin, MD, FAAN, professor of neurology at UCSF and director of the UCSF Headache Center, was somewhat skeptical of the vagus nerve stimulator when the first study was published last fall in advance of the FDA's approval. He noted in an editorial that accompanied the report in Headache that more research was needed to demonstrate the device's effectiveness in cluster headache.

In a recent interview with Neurology Today, Dr. Levin said the confirmatory results from the second study, ACT2, have now convinced him that the device has a potential place in the lineup of treatments for episodic cluster headache, but he warned against over-enthusiasm.

“Data from studies may not match results in our patients”, he said. “It will remain to be seen if people in real life get good relief.”

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DR. PETER GOADSBY said that while the response rate was less than half, “nothing works in everybody.” The device may be particularly appealing to patients because it can be used multiple times in a day, works quickly, and seems safe, he added.

Dr. Levin agreed that having more options for cluster headaches can only be a good thing. “With multiple options, we are better able to successfully pick and choose based on the individual patient,” he said.

Deborah I. Friedman, MD, MPH, FAAN, professor of neurology, neurotherapeutics and ophthalmology at University of Texas Southwestern Medical Center, said she intends to prescribe gammaCore to patients with cluster headache who aren't getting relief by other means, and who prefer a portable, non-pharmalogic, acute therapy. She was involved in testing of the device and is involved in conducting a pooled analysis of the two randomized, clinical trials.

Her medical center is also an investigation site for testing the stimulator in persons with migraine, and she has referred a number of patients to that study.

Dr. Friedman said the field of neurostimulation for headache is evolving, and she expects more devices to come along. Another approach, for instance, involves inserting a tiny stimulator through the upper gum to target a bundle of nerves called the sphenopalatine ganglion, which is involved in the generation of cluster headaches.

EXPERTS: ON A NONVASIVE VAGUS STIMULATOR FOR EPISODIC CLUSTER HEADACHE

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DR. MATTHEW S. ROBBINS said the vagus nerve stimulator “is a logistically and easier treatment modality because its this tiny hand-held device that doesnt hurt and is easily tolerated.”

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DR. MORRIS LEVIN said the device has a potential place in the lineup of treatments for episodic cluster headache, but he warned against over-enthusiasm. “Data from studies may not match results in our patients. It will remain to be seen if people in real life get good relief.”

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DR. DEBORAH I. FRIEDMAN said the field of neurostimulation for headache is evolving, and she expects more devices to come along. Another approach, for instance, involves inserting a tiny stimulator through the upper gum to target a bundle of nerves called the sphenopalatine ganglion, which is involved in migraine pain.

LINK UP FOR MORE INFORMATION:

• Mauskop A. Vagus nerve stimulation relieves chronic refractory migraine and cluster headaches http://onlinelibrary.wiley.com/doi/10.1111/j.1468-2982.2005.00611.x/full. Cephalalgia 2005;25(2):82–86.
    • Silberstein SD, Mechtler LL, Kudrow DB, et al; for the ACT1 Study Group. Non-invasive vagus nerve stimulation for the ACute Treatment of Cluster Headache: Findings from the randomized, double-blind, sham-controlled ACT1 Study http://onlinelibrary.wiley.com/doi/10.1111/head.12896/abstract. Headache 2016;56(8):1317–1332.