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

Summary

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 visit or telephone call takes place within 7 days after the second test visit. People aged 18 to 65 can take part if they have no balance disorder and meet the other study requirements. People cannot take part if, for example, they are allergic to atogepant, have taken a CGRP-blocking medicine in the past 6 months, have severe kidney or liver problems, have unstable heart disease, have a pacemaker, or are pregnant or breastfeeding. Participants are not expected to get a health benefit from taking part. The study is done to learn more about how CGRP works in the balance system, which may help in developing treatments for dizziness and migraine in the future.

Timeline

Start

2027-01-01

Primary completion

2028-12

Completion

2028-12

Publications

• Background Gianaros PJ, Muth ER, Mordkoff JT, Levine ME, Stern RM. A questionnaire for the assessment of the multiple dimensions of motion sickness. Aviat Space Environ Med. 2001 Feb;72(2):115-9.
• Background MacDougall HG, Weber KP, McGarvie LA, Halmagyi GM, Curthoys IS. The video head impulse test: diagnostic accuracy in peripheral vestibulopathy. Neurology. 2009 Oct 6;73(14):1134-41. doi: 10.1212/WNL.0b013e3181bacf85.
• Background Ailani J, Lipton RB, Goadsby PJ, Guo H, Miceli R, Severt L, Finnegan M, Trugman JM; ADVANCE Study Group. Atogepant for the Preventive Treatment of Migraine. N Engl J Med. 2021 Aug 19;385(8):695-706. doi: 10.1056/NEJMoa2035908.
• Background Edvinsson L, Haanes KA, Warfvinge K, Krause DN. CGRP as the target of new migraine therapies - successful translation from bench to clinic. Nat Rev Neurol. 2018 Jun;14(6):338-350. doi: 10.1038/s41582-018-0003-1.
• Background Jones SM, Vijayakumar S, Dow SA, Holt JC, Jordan PM, Luebke AE. Loss of alpha-Calcitonin Gene-Related Peptide (alphaCGRP) Reduces Otolith Activation Timing Dynamics and Impairs Balance. Front Mol Neurosci. 2018 Aug 24;11:289. doi: 10.3389/fnmol.2018.00289. eCollection 2018.
• Background Luebke AE, Holt JC, Jordan PM, Wong YS, Caldwell JS, Cullen KE. Loss of alpha-calcitonin gene-related peptide (alphaCGRP) reduces the efficacy of the Vestibulo-ocular Reflex (VOR). J Neurosci. 2014 Jul 30;34(31):10453-8. doi: 10.1523/JNEUROSCI.3336-13.2014.

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