BALTIMORE—When administered with standard therapy, a handheld vagal nerve stimulator significantly decreases the frequency of cluster headache attacks per week, compared with standard therapy alone, according to data presented at the 139th Annual Meeting of the American Neurological Association.
The noninvasive device, called gammaCore, was associated with seven fewer weekly headache attacks when used in conjunction with sumatriptan and oxygen. This reduction in attacks was significantly greater than the one-attack reduction achieved with standard therapy alone, said Eric Liebler, Vice President of Scientific, Medical, and Governmental Affairs at electroCore (Basking Ridge, New Jersey), the company that manufactures the device.
“In this two-month study, the external vagal nerve stimulator effected a significant improvement in the reduced rate of attacks and the 50% responder rate, with very few device-related adverse events,” he added. The device’s effects on attack pain and duration will be assessed in a separate study.
The gammaCore device is used in Europe for the treatment of primary headache disorders. The device, which transmits mild current to the vagal nerve, is a small unit that the patient uses twice per day. Researchers believe that the unit suppresses excessive extracellular glutamate in the trigeminal nucleus caudalis, a phenomenon that seems to cause trigeminal sensitization in migraine.
Patients are instructed to activate the device over the carotid pulse point on the neck for approximately 90 seconds. A conductive gel helps transmit mild current to the vagal nerve.
A Two-Month Randomized Trial
The two-month Prevention and Acute Treatment of Chronic Cluster Headache (PREVA) trial examined the use of gammaCore in treating cluster headaches. The study cohort included 97 patients who were randomized to the device plus standard therapy or to standard therapy alone. After the end of the first month, patients in the combination group continued for another month, and those in the standard-care group were offered a month of combination therapy.
The primary end point was the reduction in cluster headache attacks per week during the last two weeks of each month. Secondary end points included the number of patients with at least a 50% reduction in the number of cluster headaches per month and changes in the use of acute medications. The study also examined device safety and tolerability.
The mean age of the patients was approximately 44. Most participants (90%) were using medications and oxygen (68%), and the mean duration of their cluster headaches at baseline was about 28 minutes when they used these treatments. Without medications and oxygen, the headaches lasted for a mean of 100 minutes. These patients had approximately 70 cluster attacks in the month before randomization.
Device Reduced Use of Rescue Medications
The number of cluster headache attacks per week decreased from 16 to nine among patients in the combination group, and this reduction was statistically significant. The number of cluster headache attacks per week decreased from 16 to 15 attacks among participants taking standard therapy alone, but this difference was not statistically significant.
In the intent-to-treat population, 38% of the combination group achieved at least a 50% decrease in headache days, compared with 8% of the standard-therapy group, and this difference was statistically significant. In the full analysis, 46% of the combination group achieved this outcome, compared with 8% of the standard-therapy group. The per-protocol analysis included only patients who used the device as instructed for at least 80% of the time. The 50% responder rate in that group was 52%, compared with 9% in the standard-treatment group.
In the combination-therapy group, the use of rescue medications decreased from seven to three times per month for subcutaneous sumatriptan and from 16 to six times per month for oxygen. Both of these decreases were statistically significant. Rescue-medication use was virtually unchanged among participants who used standard therapy alone.
The device appeared to be safe and tolerable. Most of the patients using the device (44) had an adverse event. Device-related events included dizziness (3), oropharyngeal pain (3), and neck pain (3). These events probably occurred because electrical current tends to spread to neck muscles, said Mr. Liebler. These sensations were transitory.
Peter Goadsby, MD, PhD, Director of the Headache Center at the University of California, San Francisco, said that he has been “surprised” at the positive results seen in European patients who used the device. “These are medication-refractory patients, and about half of them had significant reductions in the frequency and severity of their cluster headaches, with a simultaneous decrease in the need for oxygen and steroids. They also seemed to feel that their steroids worked more efficiently” when used in conjunction with the device, he added.