SAN DIEGO — Neuromodulation of the sphenopalatine ganglion (SPG) through transnasal evaporative cooling is a promising nonpharmacologic treatment for acute migraine, results of a randomized controlled trial suggested.
The SPG, a nerve bundle located behind the nasal passages, has been implicated in migraine pathophysiology.
Mi-Helper is an investigational, semi-portable device, similar in size to sleep apnea machine, that uses dry, room-temperature air to cool the nasal cavity, which calms the SPG, relieving migraine pain and the need for medication.
“With 37 million Americans affected by migraines, the condition ranks as the second leading cause of disability globally. Clearly, there is a need for effective, safe, and drug-free treatments. Mi-Helper represents an innovative step in neuromodulation, providing a safe and well tolerated solution for those seeking better migraine relief,” study investigator MaryAnn Mays, MD, neurologist with Cleveland Clinic, Cleveland, said during a press briefing.
Mays presented the findings on April 7 at the American Academy of Neurology (AAN) 2025 annual meeting.
Promising Early Results
The trial enrolled 172 adults with episodic migraine, with 128 being treated with the study device and 74 analyzed for efficacy.
Participants were randomly allocated to self-treat a single migraine attack at home with Mi-Helper at doses of 4 liters per minute (LPM) (14 patients), 6LPM (18 patients), 10LPM (17 patients), or sham (25 patients) for 15 minutes within 1 hour of onset of pain. No other treatment was allowed within that first hour.
The primary goal was to determine the most effective dose while also assessing efficacy, safety, and tolerability.
The study found that the 10LPM dose was the most effective at relieving migraine pain, with approximately 47% of participants in this dose group achieving complete pain freedom at 2 hours compared with 16% of those in the sham group. This difference was statistically significant, Mays reported.
Additionally, more patients in the 10LPM group than the sham group had pain relief at 2 hours (71% vs 56%), although this difference was not statistically significant.
Sustained pain freedom for 24 hours without rescue medication use in the 10LPM group was numerically higher than that in the sham group (41% vs 16%).
“Importantly, the device was well tolerated, with no treatment discontinuations or serious safety events,” Mays said.
The results suggest that Mi-Helper “offers a safe, effective, and accessible option as a standalone treatment or with other existing therapies to help reduce pain of migraine and decrease reliance on medications, including opioids,” she added.
Mays noted that although studies to date have focused on migraine, the team plans to test Mi-Helper in other headache disorders and mood disorders.
Mays also noted that while the prototype device is about the size of a small sleep apnea machine, “there is interest in making smaller versions, so that you could take it with you, throw it in a bag and use it as a handheld device.”
A Breath of Fresh Air
Commenting on the research for Medscape Medical News, Shaheen Lakhan, MD, PhD, a neurologist and researcher in Miami, Florida, said the Mi-Helper device “offers a breath of fresh air in migraine treatment — literally.”
“By delivering room-temperature air through the nose to cool the sphenopalatine ganglion, it taps into a powerful neuromodulatory pathway without a single pill,” said Lakhan.
He cautioned, however, that this was a small, phase 2, dose-range finding study, not a phase 3 pivotal trial. Of the 128 patients treated, only 74 were included in the efficacy analysis — likely due to protocol deviations, incomplete data, or failure to meet predefined criteria, Lakhan noted.
“While not uncommon in early-stage trials, this limits the generalizability of the findings. Also, the statistical signals were modest, and the device itself is still bulky, requiring a power source and setup that isn’t exactly bedside-friendly,” Lakhan said.
“That said, the concept has legs, and with further refinement and validation, it could evolve into a practical option for patients seeking non-pharmacologic relief,” Lakhan told Medscape Medical News.
Briefing moderator Paul George, MD, PhD, neurologist with Stanford University in Stanford, California, and chair of the AAN science committee, said the study testing transnasal cooling for acute migraine is one of several being presented at this year’s AAN meeting that leverage “new technologies to enable new ways to treat neurologic conditions.”
George called the results “exciting” and congratulated the authors for testing a novel “nonpharmacological approach, under the biofeedback umbrella, to treat at difficult disease.”
This study was supported by Mi-Helper, Inc. Mays is an advisor to Mi-Helper and has disclosed various relationships with Pfizer, Oakley Health, AbbVie, Dynamed, and CoolTech Medical. George has served as a consultant for ConductiveBio. Lakhan had no relevant disclosures.