Effect of Atogepant on the Vestibulo-Ocular Reflex in Healthy Adults and Adults With Migraine
Trial statusNot yet recruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18-65
SponsorKonrad Peter Weber
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Age 18 to 65 years
No functional or structural vestibular disorder
No history of unilateral or bilateral vestibulopathy
No diagnosis of migraine
Disqualifiers
Hypersensitivity to atogepant
Intake of any CGRP-antagonist medication within the last 6 months
Known impaired kidney function with a creatinine clearance below 30 mL/min, or known impaired liver function (Child-Pugh B or C)
Insufficiently controlled, unstable or newly diagnosed cardiovascular disease, for example ischaemic coronary disease, coronary vasospasm or cerebral ischaemia
Trial design
Design model
Crossover
Treatments tested in this trial
Atogepant 60 mg
DrugSingle oral dose of atogepant 60 mg, administered once during the trial. The marketed Aquipta® 60 mg film-coated tablet, authorised in Switzerland, is over-encapsulated into a size 000 hard-gelatine capsule filled with mannitol (Ph. Eur.) by an independent pharmacy in order to maintain blinding; the active substance and the tablet itself are not modified. The capsule is swallowed with a glass of water under the direct supervision of the investigator, and the date and time of administration are documented.
Placebo
DrugSequence AB: Atogepant then Placebo · Sequence BA: Placebo then Atogepant
Treatment groups
80 Participants
are divided into 2 treatment groupsGroup A: Sequence AB: Atogepant then PlaceboExperimental treatment 2 interventions
Group B: Sequence BA: Placebo then AtogepantExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Change in vestibulo-ocular reflex (VOR) gain measured by video head impulse test (vHIT)
VOR gain of the horizontal semicircular canals, measured by video head impulse test as the ratio of eye velocity to head velocity (unitless), under atogepant 60 mg compared with placebo. The intra-individual difference between the atogepant condition and the placebo condition is the quantity of interest. A difference of 0.10 in VOR gain is considered clinically meaningful.
Time frame
Assessed 90-120 minutes after dosing in each of the two treatment periods (Visit 1 and Visit 2, separated by a washout of at least 5 days)Secondary outcomes
1
Caloric response
Total caloric response, calculated as the sum of the peak slow-phase eye velocities (°/s) of the four irrigations (warm and cool, left and right ear), under atogepant 60 mg compared with placebo.
Time frame
Assessed 90-120 minutes after dosing in each of the two treatment periods (Visit 1 and Visit 2, separated by a washout of at least 5 days)2
Rotary chair VOR gain (sinusoidal harmonic acceleration)
VOR gain during sinusoidal harmonic acceleration on the rotary chair (ratio of eye velocity to chair velocity, unitless), measured across the frequency range 0.01-0.5 Hz, under atogepant 60 mg compared with placebo.
Time frame
Assessed 90-120 minutes after dosing in each of the two treatment periods (Visit 1 and Visit 2, separated by a washout of at least 5 days)3
Nausea assessed by visual analogue scale
Description: Severity of nausea, assessed on a 100 mm visual analogue scale anchored at "no nausea" (0 mm) and "worst imaginable nausea" (100 mm), with higher scores indicating more severe nausea. The change from before to after the vestibular test battery is compared between the atogepant 60 mg condition and the placebo condition.
Time frame
Immediately before and immediately after the vestibular test battery at each of the two treatment visits (approximately 90 and 180 minutes after dosing)4
Motion sickness symptoms assessed by the Motion Sickness Assessment Questionnaire (MSAQ)
Motion sickness symptoms following caloric and rotary chair testing, assessed with the Motion Sickness Assessment Questionnaire (MSAQ). The MSAQ total score is reported as a percentage of the maximum possible score, with higher scores indicating more severe symptoms. The change from before to after the vestibular test battery is compared between the atogepant 60 mg condition and the placebo condition.
Time frame
Immediately before and immediately after the vestibular test battery at each of the two treatment visits (approximately 90 and 180 minutes after dosing)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Konrad Peter Weber
Lead sponsor
University of Zurich
Sponsor institution
Source ClinicalTrials.gov
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