Intranasal Temperature Modulation Device in Awake Healthy Volunteers: A First In-Human Safety and Tolerability Study

Fever after brain injury is a known contributor to poor outcomes; however, temperature-modulating devices (TMDs), such as surface and intravascular systems, face significant limitations, including delayed deployment, invasiveness, patient discomfort, skin integrity issues, frequent induction of shivering, and the need for sedation, all of which hinder timely neuroprotective therapy and confound neurological assessments. This first in-human study evaluated the safety and tolerability of an intranasal TMD, which delivers thermoelectrically temperature-regulated air via a nasal cannula to affect the core temperature. Five healthy, awake adult volunteers (median age 34 years old, 57.1% men) underwent intranasal cooling with 5°C cooled air delivered at flow rates between 15 and 58 liters per minute. The primary endpoints were safety and tolerability. The reduction in core body temperature was recorded using an esophageal temperature probe. No pharmacological agents or sedatives were administered to the patient. All participants exhibited a consistent downward trend in core body temperature, with an average reduction of 0.7°C at 30 minutes and 1.2°C at 60 minutes. Notably, no shivering or adverse events related to the intranasal TMD were reported. Cooling was well-tolerated, with esophageal probe placement being the only limiting factor for full protocol completion in some subjects. Participants remained fully conscious and communicative throughout the therapy. This intranasal TMD achieved clinically relevant core cooling without triggering shivering or requiring sedation, thereby addressing the key barriers associated with traditional TMDs. These promising early results support further investigation of this intranasal TMD in patients with acute neurological injury. Future studies should explore its performance in critical care and prehospital environments, where time-sensitive neuroprotection is most impactful.