Non-Invasive Vagus Nerve Stimulation for the ACute Treatment of Cluster Headache: Findings From the Randomized, Double-Blind, Sham-Controlled ACT1 Study.
OBJECTIVE
To evaluate non-invasive vagus nerve stimulation (nVNS) as an acute cluster headache (CH) treatment.


BACKGROUND
Many patients with CH experience excruciating attacks at a frequency that is not sufficiently addressed by current symptomatic treatments.


METHODS
One hundred fifty subjects were enrolled and randomized (1:1) to receive nVNS or sham treatment for ≤1 month during a double-blind phase; completers could enter a 3-month nVNS open-label phase. The primary end point was response rate, defined as the proportion of subjects who achieved pain relief (pain intensity of 0 or 1) at 15 minutes after treatment initiation for the first CH attack without rescue medication use through 60 minutes. Secondary end points included the sustained response rate (15-60 minutes). Subanalyses of episodic cluster headache (eCH) and chronic cluster headache (cCH) cohorts were prespecified.


RESULTS
The intent-to-treat population comprised 133 subjects: 60 nVNS-treated (eCH, n = 38; cCH, n = 22) and 73 sham-treated (eCH, n = 47; cCH, n = 26). A response was achieved in 26.7% of nVNS-treated subjects and 15.1% of sham-treated subjects (P = .1). Response rates were significantly higher with nVNS than with sham for the eCH cohort (nVNS, 34.2%; sham, 10.6%; P = .008) but not the cCH cohort (nVNS, 13.6%; sham, 23.1%; P = .48). Sustained response rates were significantly higher with nVNS for the eCH cohort (P = .008) and total population (P = .04). Adverse device effects (ADEs) were reported by 35/150 (nVNS, 11; sham, 24) subjects in the double-blind phase and 18/128 subjects in the open-label phase. No serious ADEs occurred.


CONCLUSIONS
In one of the largest randomized sham-controlled studies for acute CH treatment, the response rate was not significantly different (vs sham) for the total population; nVNS provided significant, clinically meaningful, rapid, and sustained benefits for eCH but not for cCH, which affected results in the total population. This safe and well-tolerated treatment represents a novel and promising option for eCH. ClinicalTrials.gov identifier: NCT01792817.
Department of Neurology, Jefferson Headache Center, Philadelphia, PA, USA. stephen.silberstein@jefferson.edu.
Stephen D
SD
Silberstein
Department of Neurology and Neuro-Oncology, Dent Neurologic Headache Center, Amherst, NY, USA.
Laszlo L
LL
Mechtler
California Medical Clinic for Headache, Santa Monica, CA, USA.
David B
DB
Kudrow
Carolina Headache Institute, Durham, NC, USA.
Anne H
AH
Calhoun
North American Science Associates Inc, Minneapolis, MN, USA.
Candace
C
McClure
Michigan Head Pain and Neurological Institute, Ann Arbor, MI, USA.
Joel R
JR
Saper
Department of Scientific, Medical and Governmental Affairs, electroCore, LLC, Basking Ridge, NJ, USA.
Eric J
EJ
Liebler
Dalessio Headache Center at Scripps Clinic, La Jolla, CA, USA.
Emily
E
Rubenstein Engel
Department of Neurology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.|Dr. Tepper was at Cleveland Clinic Headache Center, Cleveland, OH, at the time of study completion.
Stewart J
SJ
Tepper
D003027:Cluster Headache / Q000628:therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D016896:Treatment Outcome; D014481:United States; D055536:Vagus Nerve Stimulation / Q000295:instrumentation / Q000379:methods*
acute treatment; chronic cluster headache; episodic cluster headache; neuromodulation; non-invasive vagus nerve stimulation; randomized controlled trial