Kinetic Oscillation Stimulation Proves to be Therapeutically Beneficial for Chronic Migraine

Jan Hoffman, MD, PhD

Recently published data from a double-blind, sham-controlled trial (NCT03400059) showed that kinetic oscillation stimulation (KOS) using the Chordate System may provide significant therapeutic benefits to patients with chronic migraine (CM). Investigators concluded that because of its nonpharmacologic mechanism of action, it may be particularly suitable for patients who are worried about systemic adverse events (AEs).¹

Published in Neurology, the double-blind study featured 144 patients who were treated with the intranasal stimulation through the Chordate System (n = 75) once per week for 10 minutes per nostril or sham (n = 69). Patients underwent a 4-week screening period, a 6-week treatment period, and a 4-week follow-up. Led by Jan Hoffman, MD, an associate professor of neurology at Kings College London, results showed a significantly larger reduction of monthly headache days (MHD) across the performance assessment period with active treatment (–3.5 days) compared with sham (–1.2 days; P = .0132).

The Chordate System, which administers KOS into the nasal cavity, consists of the Chordate Controller, the Chordate Catheter, and the Chordate Headband. In the study, healthcare professionals inserted the balloon part of the catheter into the participants’ nasal cavity, inflating it, and stimulating the nasal mucosa with mechanical pressure and vibration at a frequency of 85 Hz (treatment group).

Regarding the KOS approach, investigators wrote that "The exact mechanism of action remains to be elucidated. Given that KOS reliably induces cranial autonomic symptoms, it is likely that it acts through a modulation of the trigemino-autonomic reflex. Considering the anatomical proximity, it may be speculated that the site of action may be around the sphenopalatine ganglion. Similarly, the involved molecular mechanisms remain unclear. An action on the parasympathetic outflow may suggest that it may influence the release of parasympathetic neuropeptides such as PACAP and VIP. However, the analysis of involved molecular mechanisms was outside of the scope of this study."

A total of 140 patients made up the full analysis set (FAS) for analysis of performance while 144 participants were included in the safety analysis set (SAF) for safety analyses. Overall, 132 participants completed the study, leaving 12 patients who discontinued prematurely. Coming into the trial, selective serotonin receptor agonists (triptans) were the most frequent concomitant medication, used by 88.2% of patients for the acute treatment of migraine. Preventive migraine medication was used by 38.2% of participants, with candesartan (active: 11.8%; sham: 8.8%) as the most common.

On secondary end points, the active treatment group showed significant reductions in monthly headache days (MHDs) during the 4-week follow-up period (–2.7; 95% CI, –4.3 to –1.0; P = .0014), as well as in the number of migraine days during the 4-week performance period (–2.4; 95% CI, –4.1 to –0.7; P = .0048) and follow-up periods (–2.9; 95% CI, –4.5 to –1.2; P =.0008). Additionally, abortive medication use was lower in the active treatment group, with a significant reduction in the follow-up period (P = 0.0152). Notably, 47% of participants in the active treatment group had a 30% reduction in MHDs during the performance assessment period, compared to only 25% in the sham group (P = 0.0148). However, this difference was less pronounced in the follow-up period (39% vs 28%, P = 0.2171).

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Overall, 61.8% of participants reported treatment-emergent adverse events (TEAEs), with a similar incidence across treatment groups. The most common TEAEs were nasopharyngitis (8.3%), dizziness (6.3%), and epistaxis (6.3%), with dizziness occurring more often in the active treatment group (9.2%) than in the sham group (2.9%). Only one serious AE, unrelated to treatment, was reported in the active group, and none occurred in the sham group. Otherwise, the incidence of TEAEs was similar between groups.

A total of 97 TEAEs in 30 participants (20.8%) were considered related to the study procedure. More procedure-related TEAEs occurred in the active group (70) compared to the sham group (27), though the number of affected participants was similar (active: 17, sham: 13). The most frequent device-related TEAEs were epistaxis and rhinorrhea. Additionally, 11 device deficiencies were reported in 7 participants, none of which led to serious adverse device effects.

Investigators concluded that, "Although a potential study limitation arises from the fact that an analysis that would assess the efficacy of blinding was not conducted at the end of the study, such an analysis was not performed because the risk of unblinding was considered to be very low. The Chordate system may therefore represent a valuable addition to the therapeutic portfolio of preventive treatments for CM, and due to its nonpharmacologic mechanism of action, it is particularly suitable for patients who are worried about systemic side effects."

REFERENCE
1. Hoffman J, Kaube H, Rimmele F, et al. Kinetic Oscillation Stimulation for the Preventive Treatment of Chronic Migraine A Randomized, Double-Blind, Sham-Controlled Trial. Neurology. 2025;104(3). doi:10.1212/WNL.0000000000210220