Vagal Nerve Stimulation Stops Episodic Cluster Headache Pain

Daniel M. Keller, PhD

September 20, 2017

VANCOUVER, Canada — Noninvasive vagus nerve stimulation (nVNS) relieves pain for patients with episodic but not chronic cluster headache, new research suggests.

This treatment modality may have advantages over current options, such as triptans, which are contraindicated for patients with cardiovascular disease, or inhaled oxygen, which may not always be available, note the investigators.

Ilse de Coo, MD, Leiden University Medical Center, the Netherlands, presented results of the Non-invasive Vagus Nerve Stimulation for the Acute Treatment of Episodic and Chronic Cluster Headache (ACT2) trial here at the 18th Congress of the International Headache Society (IHC) 2017.  

The device used for stimulation in this trial, gammaCore (electroCore LLC), was approved by the US Food and Drug Administration in April for the treatment of pain from episodic cluster headache. Approval was based on the ACT2 and ACT1 trials, both of which were sponsored by electroCore.

The randomized, double-blind, sham-controlled ACT2 study used a 1-week run-in period, then a 2-week intervention period of nVNS or sham stimulation. This was followed by a 2-week open-label period in which all participants received nVNS.

When an attack occurred, treatment consisted of three consecutive real or sham 120-second stimulations over 6 minutes, followed by a 3-minute pause and then an optional set of three consecutive stimulations or sham stimulations as in the first set. Pain intensity was assessed at 15 minutes.

In the double-blind phase, the nVNS group included 50 patients, with 52 in the sham group. Of these, 30 had episodic and 72 had chronic cluster headaches. The groups were well balanced for age (early to mid-40s); approximately 70% were male, and  just about all were white. The mean number of cluster headache attacks ranged from 69.6 to 76.1 during the run-in period.

VNS: Effective and Safe

For patients with episodic cluster headaches, significantly more attacks met the primary endpoint of complete relief of pain at 15 minutes after using nVNS compared with sham stimulation (47.5% of 101 attacks vs 6.2% of 81 attacks, respectively; P < .01).

No significant differences occurred for patients with chronic cluster headaches; 4.8% of 294 attacks with nVNS vs 12.9% of 319 attacks with sham stimulation achieved freedom from pain (P = .13).

The patients with episodic headaches also had a greater decrease from baseline in the mean pain intensity score on a 0 to 4 scale with nVNS (change, –1.7) than with sham (–0.6; P = .01). There was no statistically significant difference in pain intensity scores for patients with chronic cluster headaches with use of nVNS or sham stimulation (P = .52).

Dr de Coo said the interventions were safe and well tolerated, even with 40% of the nVNS group and 26.9% of the sham controls reporting any adverse event. Skin and subcutaneous disorders or musculoskeletal and connective tissue disorders affected no more than 4% of either group.

She said this study is "the second randomized clinical trial to show nVNS is a safe and effective acute treatment option for episodic cluster headache." However, it was ineffective for chronic cluster headache.

"Promising" Option

Session moderator Patricia Pozo-Rosich, MD, PhD, Vall d'Hebron University Hospital, Barcelona, Spain, said that nVNS provides a new opportunity for patients with cluster headache. Most focus in the headache field has been on migraines, she said, "so having other options for these patients I think is nice and promising and something to move the field forward."

One limitation of the study is that it was "very brief," she said, with blinded treatment for only 2 weeks before transitioning to open label. "The big thing with any type of these devices is the lack of secondary potentially adverse events or high-risk adverse events, and that is always also good, so it's positive."

When asked whether anyone knows exactly what electrical stimulation is doing physiologically, Dr Pozo-Rosich said the company is using animal models to investigate the basis of the effect: whether the stimulation is modifying the underlying biology of the condition, whether it is just treating the acute pain, or whether it may have a preventive effect.

Dr de Coo has received travel grants from electroCore, which sponsored the study. Dr Pozo-Rosich participated in a trial involving vagal nerve stimulation for the treatment of episodic migraines, for which she received no honoraria and held no position with the sponsoring company.

18th Congress of the International Headache Society (IHC) 2017. Abstract OC-MC-003. Presented September 9, 2017.

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