Cluster Headache Treatment Research: New Horizons

Thursday, June 15, 2017 

Noninvasive Vagus Nerve Stimulation Interrupts Episodic but Not Chronic Cluster Headache

​BY RICHARD ROBINSON

Noninvasive vagus nerve stimulation provides significant acute relief from episodic, but not chronic, cluster headache attacks, according to combined results from two double-blind, sham-controlled studies, presented here on June 10 at the American Headache Society annual meeting.

The stimulating device, called GammaCore, is a handheld, portable device that is placed against the neck and delivers mild electrical stimulation. Patients with chronic cluster headache have attacks that occur daily for more than a year with remissions of less than 14 days between attacks. About 20 percent of cluster headache patients have the chronic form.

Together, the two trials (called ACT1 and ACT2) enrolled 252 patients with episodic (n=131) and chronic (n=121) cluster headache, about 75 percent male, mostly white, with headache duration of over 12 years. Patients in both trials were randomized 1:1 to sham stimulation or active stimulation, delivered in multiple two-minute treatments at the onset of an attack. The number of treatments per attack was three in ACT1 (for a total of six-minutes stimulation) and six in ACT2 (12-minutes stimulation). Patients were asked to refrain from using other rescue treatments for the first 15 minutes after the onset of an attack. The primary endpoint in ACT1 was degree of response after 15 minutes for the first attack, while for ACT2 it was the percentage of all attacks in a two-week period that were pain-free at 15 minutes.

Individually, both trials met their primary endpoints for patients, but were not powered to distinguish benefit for episodic versus chronic headache. In the pooled data, in episodic patients, 24 percent of all treated attacks were pain-free at 15 minutes for real stimulation, versus 7 percent for placebo (p<0.01). In patients with chronic cluster headache, no significant difference was reported between real and sham stimulation in either trial, or in the pooled data. Forty-two percent of episodic patients receiving real stimulation had significant pain reduction at 15 minutes in at least 50 percent of their attacks, versus 15 percent of sham-treated patients. Again, there was no difference in response rate for chronic patients. Adverse events were similar between real and sham groups.

The reasons for the difference in response between episodic and chronic headache patients are not clear, according to Eric Liebler, vice president of scientific, medical, and governmental affairs for ElectroCore, which developed the device. "We are going to continue to investigate the reasons for this, which may in turn give us some insight into the pathogenesis of cluster headache," he said.

The device was cleared by the US Food and Drug Administration in April, and will be available beginning in July.

"Vagal nerve stimulation appears to be a potentially promising acute treatment of episodic cluster headache," said Morris Levin, MD, FAAN, professor of neurology and director of the UCSF Headache Center at the University of California at San Francisco, who was not involved in the study. While many patients respond well to preventive treatments, such as steroids, lithium, and calcium channel blockers, acute treatment of emergent attacks has for many patients been more challenging. Triptans may be effective but are limited in the number of daily attacks they may be used for, while oxygen may be used without limit, but requires keeping a tank near at hand.

"I think the GammaCore device has real potential," Dr. Levin added, but as with any new treatment, it will take time to see how well the data from the trial are mirrored in clinical practice.

LINK UP FOR RELATED INFORMATION:

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. Headache 2016;56(8):1317-1332.