Pathway ch-1 study: sphenopalatine ganglion (spg) stimulation for acute treatment of chronic cluster headache (CCH)

Introduction

The pain and autonomic symptoms of cluster headache result from activation of the trigeminal parasympathetic reflex, mediated through the SPG [1, 2]. We aimed to investigate the safety and efficacy of SPG stimulation for the acute treatment of CCH.

Methods

A multi-center, dose range finding, multiple headache attack (HA), acute treatment study with random insertion of placebo was initiated. All subjects met the ICHD-2 criteria for CCH with a minimum of 4 HA/week. Subjects were implanted with a miniaturized neurostimulator which, along with a controller, provides on-demand SPG stimulation. During the blinded experimental period (EXP), each HA was randomly treated with 1 of 3 therapies: full, sub-perception or placebo stimulation. Pain relief at15 minutes (decrease from ‘moderate’ or ‘severe’ to ‘none’ or ‘mild’ on the 5-point scale) and HA frequency reduction were analyzed.

Results

Thirty-two subjects were enrolled, 27 completed the EXP. One subject remains in EXP, 1 skipped EXP, 2 were explanted due to early lead migration, and 1 did not complete the implant due to difficult anatomy. Pain relief was achieved in 67% of HA (n=190) treated with full compared to 8% (n=183) with sub-perception and 8% (n=189) with placebo stimulation. A clinically significant improvement occurred in 19 of 27 (70%) subjects: 7 (26%) achieved acute pain relief in ≥50% of treated HAs, 10 (37%) a ≥50% reduction in HA frequency compared to baseline and 2 (7%) experienced both. Of the 12 frequency responders, HA frequency was reduced to ≤2 HA/week in 9 subjects. Eight (29%) of the 27 did not respond or did not provide sufficient data for evaluation. Most subjects (47%) experienced transient, mild to moderate numbness within the second division of the trigeminal nerve post implant with 62% resolving within the first three months.

Conclusions

Results suggest that acute, on-demand SPG stimulation using the ATI Neurostimulation System has acute and preventive effects and is an effective novel therapy for CCH. In this study, 70% of subjects responded to the therapy.