Migraine Disorders, BrainPhase 4VOR-GRIPNCT07826910
Effect of Atogepant on the Vestibulo-Ocular Reflex in Healthy Adults and Adults With Migraine
A Phase 4 study testing Atogepant 60 mg in people with Migraine Disorders, Brain and Healthy Adult Participants, run by Konrad Peter Weber at 1 site in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Migraine Disorders, Brain, Healthy Adult Participants, Vestibulo-Ocular Reflex
- What is being tested?
- Atogepant 60 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteSwitzerland
- Study dates
- 1 Jan 2027to Dec 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy participants (Phase 1 of enrolment):
- Age 18 to 65 years
- No functional or structural vestibular disorder
- No history of unilateral or bilateral vestibulopathy
- No diagnosis of migraine
- Written informed consent provided by the participant
Show all 12Show fewer
- Participants with migraine (Phase 2 of enrolment):
- Diagnosis of episodic or chronic migraine according to the ICHD-3 criteria
- Age 18 to 65 years
- No functional or structural vestibular disorder
- No history of unilateral or bilateral vestibulopathy
- Written informed consent provided by the participant
Who cannot join
- 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
- Myocardial infarction, acute coronary syndrome, percutaneous coronary intervention, cardiac surgery, stroke of any kind or transient ischaemic attack within the last 6 months (24 weeks)
- Medication overuse headache
Show all 11Show fewer
- Cardiac pacemaker or other implanted electronic device
- Concomitant use of strong CYP3A4 inhibitors, of strong or moderate CYP3A4 inducers, or of OATP1B1/OATP1B3 inhibitors
- Pregnancy or breastfeeding; women of childbearing potential not using effective contraception during the study
- Participation in another clinical trial with an investigational medicinal product within 30 days before the screening visit
- Inability to understand the participant information or to give written informed consent
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Switzerland1 site
University Hospital Zurich, Department of Neurology
Zurich, Canton of Zurich, 8091
Vergil V Mavrodiev, MD, +41 43 253 64 03, Vergil.Mavrodiev@usz.ch
Ricarda Wurm, MD, +41 43 253 03 65, Ricarda.Wurm@usz.ch
About this study
Official title: The Role of CGRP in Human Vestibulo-Ocular Reflex (VOR) - a Randomized, Blinded, Placebo-controlled, Cross-over 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.
Read more
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.
Read the detailed description
Background and rationale
Calcitonin gene-related peptide (CGRP) is a neuropeptide with an established role in migraine pathophysiology, and CGRP receptor antagonists (gepants) are approved for migraine treatment and prevention. CGRP is also expressed in the vestibular periphery, where it is released by efferent neurons onto type II hair cells and calyx-bearing afferents. Mice lacking the CGRP gene or the CGRP receptor show reduced VOR gain, indicating that CGRP contributes to the sensitivity of the vestibular afferent response. Whether CGRP receptor antagonism produces a comparable reduction of VOR gain in humans has not been investigated. Because gepants are now widely prescribed, the question is of practical as well as mechanistic relevance, and it may also inform the pathophysiology of vestibular migraine.
Objective
The trial investigates whether acute pharmacological blockade of the CGRP receptor reduces the gain of the vestibulo-ocular reflex in humans. Semicircular canal function is assessed across the frequency spectrum (video head impulse test, caloric irrigation, sinusoidal harmonic acceleration on the rotary chair) and otolith function is assessed by the ocular counter-torsion response to static whole-body tilt. Prepulse inhibition of the blink reflex is assessed as an additional brainstem excitability measure.
Design
Single-centre, randomised, placebo-controlled, double-blind, two-period cross-over trial conducted in two consecutive phases: 40 healthy participants are enrolled first, and recruitment of 40 participants with episodic or chronic migraine (ICHD-3) begins only once enrolment in the healthy group is complete. Total enrolment is 80.
Each participant attends a screening visit (Visit 0, up to 28 days before or on the same day as Visit 1), two treatment visits (Visits 1 and 2) separated by a washout period of at least 5 days, and a safety follow-up (Visit 3) within 7 days after Visit 2. Each treatment visit lasts approximately 165 minutes.
Randomisation and blinding
Participants are randomised 1:1 to treatment sequence AB (atogepant at Visit 1, placebo at Visit 2) or BA. The allocation sequence is computer-generated with permuted blocks of variable length, stratified by group, by a physician independent of the study team who holds the random seed, the block lengths and the master code list and who releases the list only after database lock. Blinded kits are prepared and labelled to that sequence by an independent pharmacy. Participants, the sponsor-investigator, the sub-investigators, the study staff, the statistician and the monitor all remain blinded. One sealed code-break envelope per participant is held at the site for emergency unblinding.
Intervention
A single oral dose of atogepant 60 mg, or matching placebo, is administered under direct supervision at each treatment visit. To preserve the blind, the marketed film-coated tablet is over-encapsulated in a size 000 hard-gelatine capsule filled with mannitol; the placebo capsule contains mannitol only and is identical in appearance. The 5-day washout exceeds ten elimination half-lives of atogepant (t½ ≈ 11 h). Vestibular testing begins 90-120 minutes after dosing, and participants remain under observation at the site for at least 90 minutes after each dose.
Statistical analysis
The primary null hypothesis is that the mean intra-individual difference in VOR gain between the atogepant and placebo conditions is zero, tested two-sided at α = 0.05. Analyses use paired t-tests and repeated-measures ANOVA for within-group comparisons and mixed-effects models for comparisons between the healthy and migraine groups, accounting for the cross-over design. Sex is included as a covariate.
Oversight
Investigator-initiated trial, Category B under the Swiss Clinical Trials Ordinance. No Data Monitoring Committee is established; the rationale is given in the protocol. Risk-adapted monitoring is performed by an independent, blinded monitor.
- Being tested
- Atogepant 60 mg, Placebo
- Keywords
- CGRP, Calcitonin Gene-Related Peptide, CGRP receptor antagonist, Gepant, Atogepant, Vestibulo-ocular reflex, VOR gain, Vestibular function, Otolith function, Video head impulse test, vHIT, Caloric testing, Rotary chair, Sinusoidal harmonic acceleration, Prepulse inhibition, Blink reflex, Cross-over study, Healthy volunteers, Migraine
- Medical subject headings
- Migraine Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Atogepant 60 mgDrug
Also called Aquipta, Qulipta
Single 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.
PlaceboDrug
Sequence AB: Atogepant then Placebo · Sequence BA: Placebo then Atogepant
| Study group | Role | What they receive |
|---|---|---|
| Sequence AB: Atogepant then Placebo | Experimental | Drug: Atogepant; Drug: Placebo Receives: Drug: Atogepant 60 mg; Drug: Placebo |
| Sequence BA: Placebo then Atogepant | Experimental | Drug: Placebo; Drug: Atogepant Receives: Drug: Atogepant 60 mg; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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 (8)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: Immediately before and immediately after the vestibular test battery at each of the two treatment visits (approximately 90 and 180 minutes after dosing)
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.
Measured: Immediately before and immediately after the vestibular test battery at each of the two treatment visits (approximately 90 and 180 minutes after dosing)
Spinning vertigo assessed by visual analogue scale
Severity of spinning vertigo, assessed on a 100 mm visual analogue scale anchored at "no spinning vertigo" (0 mm) and "worst imaginable spinning vertigo" (100 mm), with higher scores indicating more severe vertigo. The change from before to after the vestibular test battery is compared between the atogepant 60 mg condition and the placebo condition.
Measured: Immediately before and immediately after the vestibular test battery at each of the two treatment visits (approximately 90 and 180 minutes after dosing)
VOR latency
Latency (milliseconds) between the onset of the head movement and the onset of the compensatory eye movement during video head impulse testing, under atogepant 60 mg compared with placebo.
Measured: 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)
Compensatory saccades
Presence and characteristics of compensatory overt and covert saccades during video head impulse testing, under atogepant 60 mg compared with placebo.
Measured: 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)
Prepulse inhibition of the blink reflex
Prepulse inhibition of the blink reflex, expressed as the percentage reduction of the blink reflex response amplitude when preceded by a prepulse stimulus, under atogepant 60 mg compared with placebo.
Measured: Time Frame: 90-150 minutes after dosing in each treatment period.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2026
- Study start1 Jan 2027 (estimated)
- Primary completionDec 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Migraine Disorders, BrainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Two-period, two-sequence (AB/BA) cross-over design. Each participant receives a single oral dose of atogepant 60 mg in one period and a single oral dose of matching placebo in the other, separated by a washout period of at least 5 days. The trial is conducted in two consecutive phases: 40 healthy participants are enrolled first, and enrolment of 40 participants with episodic or chronic migraine begins only after enrolment in the healthy group is complete. Randomisation is stratified by group, so allocation is balanced within each phase.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Konrad Peter Weber
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Konrad Peter Weber, University of Zurich
- Investigators
- Konrad P Weber, Prof., Principal investigator, University Hospital Zurich, Department of Neurology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07826910
- Sponsor's protocol ID
- BASEC 2024-02190
- Acronym
- VOR-GRIP
- Status last verified
- Sep 2026
- First submitted
- 10 Sep 2026
- Last updated
- 17 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be shared. The participant information and informed consent form for this investigator-initiated, single-centre trial do not cover the further use of the collected data for research purposes beyond this project, and under the Swiss Human Research Act data may not be shared for purposes that are not covered by the participants' consent. In addition, the dataset is small (80 participants from a single centre) and contains detailed oculomotor and clinical measurements, so a meaningful risk of re-identification would remain after de-identification.
Publications
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.
PubMed 11211039MacDougall 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.
PubMed 19805730Ailani 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.
PubMed 34407343Edvinsson 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.
PubMed 29691490Jones 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.
PubMed 30197585Luebke 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.
PubMed 25080603
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of CGRP in Human Vestibulo-Ocular Reflex (VOR) - a Randomized, Blinded, Placebo-controlled, Cross-over Trial
- ClinicalTrials.gov ID
- NCT07826910
- Acronym / sponsor ID
- VOR-GRIP / BASEC 2024-02190
- Keywords
- CGRP, Calcitonin Gene-Related Peptide, CGRP receptor antagonist, Gepant, Atogepant, Vestibulo-ocular reflex, VOR gain, Vestibular function
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Konrad Peter WeberUniversity, hospital or other
- Study start
- 1 Jan 2027 (estimated)
- Primary completion
- Dec 2028 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 17 Sep 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Background and rationale
Calcitonin gene-related peptide (CGRP) is a neuropeptide with an established role in migraine pathophysiology, and CGRP receptor antagonists (gepants) are approved for migraine treatment and prevention. CGRP is also expressed in the vestibular periphery, where it is released by efferent neurons onto type II hair cells and calyx-bearing afferents. Mice lacking the CGRP gene or the CGRP receptor show reduced VOR gain, indicating that CGRP contributes to the sensitivity of the vestibular afferent response. Whether CGRP receptor antagonism produces a comparable reduction of VOR gain in humans has not been investigated. Because gepants are now widely prescribed, the question is of practical as well as mechanistic relevance, and it may also inform the pathophysiology of vestibular migraine.
Objective
The trial investigates whether acute pharmacological blockade of the CGRP receptor reduces the gain of the vestibulo-ocular reflex in humans. Semicircular canal function is assessed across the frequency spectrum (video head impulse test, caloric irrigation, sinusoidal harmonic acceleration on the rotary chair) and otolith function is assessed by the ocular counter-torsion response to static whole-body tilt. Prepulse inhibition of the blink reflex is assessed as an additional brainstem excitability measure.
Design
Single-centre, randomised, placebo-controlled, double-blind, two-period cross-over trial conducted in two consecutive phases: 40 healthy participants are enrolled first, and recruitment of 40 participants with episodic or chronic migraine (ICHD-3) begins only once enrolment in the healthy group is complete. Total enrolment is 80.
Each participant attends a screening visit (Visit 0, up to 28 days before or on the same day as Visit 1), two treatment visits (Visits 1 and 2) separated by a washout period of at least 5 days, and a safety follow-up (Visit 3) within 7 days after Visit 2. Each treatment visit lasts approximately 165 minutes.
Randomisation and blinding
Participants are randomised 1:1 to treatment sequence AB (atogepant at Visit 1, placebo at Visit 2) or BA. The allocation sequence is computer-generated with permuted blocks of variable length, stratified by group, by a physician independent of the study team who holds the random seed, the block lengths and the master code list and who releases the list only after database lock. Blinded kits are prepared and labelled to that sequence by an independent pharmacy. Participants, the sponsor-investigator, the sub-investigators, the study staff, the statistician and the monitor all remain blinded. One sealed code-break envelope per participant is held at the site for emergency unblinding.
Intervention
A single oral dose of atogepant 60 mg, or matching placebo, is administered under direct supervision at each treatment visit. To preserve the blind, the marketed film-coated tablet is over-encapsulated in a size 000 hard-gelatine capsule filled with mannitol; the placebo capsule contains mannitol only and is identical in appearance. The 5-day washout exceeds ten elimination half-lives of atogepant (t½ ≈ 11 h). Vestibular testing begins 90-120 minutes after dosing, and participants remain under observation at the site for at least 90 minutes after each dose.
Statistical analysis
The primary null hypothesis is that the mean intra-individual difference in VOR gain between the atogepant and placebo conditions is zero, tested two-sided at α = 0.05. Analyses use paired t-tests and repeated-measures ANOVA for within-group comparisons and mixed-effects models for comparisons between the healthy and migraine groups, accounting for the cross-over design. Sex is included as a covariate.
Oversight
Investigator-initiated trial, Category B under the Swiss Clinical Trials Ordinance. No Data Monitoring Committee is established; the rationale is given in the protocol. Risk-adapted monitoring is performed by an independent, blinded monitor.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Two-period, two-sequence (AB/BA) cross-over design. Each participant receives a single oral dose of atogepant 60 mg in one period and a single oral dose of matching placebo in the other, separated by a washout period of at least 5 days. The trial is conducted in two consecutive phases: 40 healthy participants are enrolled first, and enrolment of 40 participants with episodic or chronic migraine begins only after enrolment in the healthy group is complete. Randomisation is stratified by group, so allocation is balanced within each phase.
| Arm | Type | Receives |
|---|---|---|
| Sequence AB: Atogepant then Placebo | Experimental | Drug: Atogepant 60 mg, Drug: PlaceboDrug: Atogepant; Drug: Placebo |
| Sequence BA: Placebo then Atogepant | Experimental | Drug: Atogepant 60 mg, Drug: PlaceboDrug: Placebo; Drug: Atogepant |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Age 18 to 65 years
- No functional or structural vestibular disorder
- No history of unilateral or bilateral vestibulopathy
- No diagnosis of migraine
- Written informed consent provided by the participant
Key exclusion criteria (11 listed)
- 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
- Myocardial infarction, acute coronary syndrome, percutaneous coronary intervention, cardiac surgery, stroke of any kind or transient ischaemic attack within the last 6 months (24 weeks)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Atogepant 60 mgAlso: Aquipta, QuliptaSingle 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. | Drug | Sequence AB: Atogepant then Placebo, Sequence BA: Placebo then Atogepant |
| PlaceboSequence AB: Atogepant then Placebo · Sequence BA: Placebo then Atogepant | Drug | Sequence AB: Atogepant then Placebo, Sequence BA: Placebo then Atogepant |
Primary outcome
Change in vestibulo-ocular reflex (VOR) gain measured by video head impulse test (vHIT)
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)
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.
8 secondary outcomes
Caloric response
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)
Rotary chair VOR gain (sinusoidal harmonic acceleration)
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)
Nausea assessed by visual analogue scale
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)
Motion sickness symptoms assessed by the Motion Sickness Assessment Questionnaire (MSAQ)
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)
Spinning vertigo assessed by visual analogue scale
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)
VOR latency
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)
Compensatory saccades
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)
Prepulse inhibition of the blink reflex
Time frame: Time Frame: 90-150 minutes after dosing in each treatment period.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2026.
- Background: PubMed 11211039Gianaros 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: PubMed 19805730MacDougall 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: PubMed 34407343Ailani 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: PubMed 29691490Edvinsson 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: PubMed 30197585Jones 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: PubMed 25080603Luebke 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.
- Individual participant dataSharing planned: No. Individual participant data will not be shared. The participant information and informed consent form for this investigator-initiated, single-centre trial do not cover the further use of the collected data for research purposes beyond this project, and under the Swiss Human Research Act data may not be shared for purposes that are not covered by the participants' consent. In addition, the dataset is small (80 participants from a single centre) and contains detailed oculomotor and clinical measurements, so a meaningful risk of re-identification would remain after de-identification.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Konrad P Weber, Prof. principal investigator
University Hospital Zurich, Department of Neurology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Atogepant 60 mg in people with Migraine Disorders, Brain and Healthy Adult Participants, run by Konrad Peter Weber at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 17 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Vergil V Mavrodiev, MD (+41 43 253 64 03, Vergil.Mavrodiev@usz.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in vestibulo-ocular reflex (VOR) gain measured by video head impulse test (vHIT) (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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07826910, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2026.