Effect of Atogepant on the Vestibulo-Ocular Reflex in Healthy Adults and Adults With Migraine

Researchers want to find out how a substance in the body called CGRP affects balance. CGRP (calcitonin gene-related peptide) is a small protein involved in migraine. Several approved migraine medicines work by blocking it. Studies in animals suggest that CGRP also helps a reflex called the vestibulo-ocular reflex, or VOR. The VOR keeps vision steady when the head moves: when the head turns, the eyes move the opposite way by the same amount, so the world does not appear to jump. Animals that lack the CGRP receptor have a weaker VOR. It is not known whether blocking CGRP weakens the VOR in people. This study tests whether a single dose of atogepant changes the VOR in people. Atogepant is approved in Switzerland for the prevention of migraine and blocks the CGRP receptor. In this study it is used in a different way than it is approved for. Eighty people will take part at the University Hospital Zurich. The study runs in two parts. First, 40 healthy people join. After that, 40 people who have episodic or chronic migraine join. Everyone receives both of the following, in random order: one capsule containing atogepant 60 mg one capsule containing placebo (a capsule with no active medicine) The two test visits are at least 5 days apart. A computer decides which capsule each person receives first. Neither the participants nor the study team know which capsule is which until the study is finished. At each test visit, the participant swallows the capsule at the study centre and stays for at least 90 minutes. Balance and eye-movement tests then begin, about 90 to 120 minutes after the capsule. The tests record eye movements while the head is moved quickly, while warm and cool air or water is placed in the ear canal, while a chair turns gently from side to side, and while the whole body is tilted. Participants also answer short questionnaires about nausea and dizziness before and after the tests. Each test visit lasts about 2 hours and 45 minutes. A short follow-up visi