The R-E-V-I-V-A-L Study

NCT06992674 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: 2025-0124
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

Brief Summary

Vestibular migraine (VM) is one of the most common vestibular disorders, affecting 1.0% to 2.7% of the general population1, 7% of patients with definite migranous vertigo in dizziness clinics2, as well as 10.3% of VM patients in headache clinics3; 65% to 85% of VM patients are female1. Despite the relative prevalence of vestibular migraine, evidence-based medicine remains scarce. Two Cochrane reviews published in 2023 found that there is almost no evidence to support the use of medications for the acute treatment or preventive treatment of VM4,5. Calcitonin gene-related peptide (CGRP) has been established as an excellent target for the treatment of migraine. Animal studies suggest a link between CGRP and vestibular disorders. A prospective observational cohort study found that monoclonal antibodies targeting CGRP receptors and ligands were very effective for vestibular migraine (VM), with 90% of participants experiencing at least a 50% reduction in vertigo attacks6. A small-scale prospective randomized controlled trial showed that a monoclonal antibody targeting a CGRP ligand significantly reduced the number of dizziness days per month in VM patients compared to placebo7. The efficacy of CGRP small molecule antagonists for the preventive and acute treatment of migraines has been widely recognized8,9. Therefore, we speculate that Rimegepant is effective for the preventive and acute treatment of vestibular migraine. By focusing on a large sample RCT, our study can offer new evidence-based treatment options for patients with vestibular migraine. This is crucial, as many patients with vestibular migraine may not respond well to conventional migraine treatments. Our findings could guide clinicians in choosing more effective therapeutic strategies. Specifically in acute treatment of vestibular migraine, triptans have failed to show superiority when compared to placebo in treatment vestibular migraine symptoms10. Prochlorperazine, a vestibular sedative, is widely used for acute treatment of vestibular migraine but is known to chronify symptoms11. Should rimegepant demonstrate superiority to placebo in this study, rimegepant could potentially become the first-line treatment for vestibular migraine across the world.

Conditions

Vestibular Migraine

Outcome Measures

Primary Outcomes (1)

• Moderate/Severe vestibular symptom days

  Change in number of Moderate/Severe vestibular symptom days as defined by Barany Society1 for participants measured daily from the observational phase compared to weeks 12-16.

  from baseline to weeks 12-16

Secondary Outcomes (11)

• Moderate/Severe vestibular symptom days

  every 4 weeks during the 12-week treatment period compared to baseline

• the number of vestibular symptom attacks

  every 4 weeks compared to baseline over the 12-week treatment period

• MMD

  every 4 weeks compared to baseline over the 12-week treatment period

• MIDAS

  from baseline to week 16

• percentage reduction in moderate/severe vestibular symptom days

  from baseline to weeks 12-16

Study Arms (2)

Group A1:Rimegepant ODT 75mg, EOD

EXPERIMENTAL

Drug: Rimegepant

Group A2: Placebo, QD

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Rimegepant DRUG

Take 75mg qd of oral sulfate remigipan orally disintegrating tablets

Group A1:Rimegepant ODT 75mg, EOD

Placebo DRUG

Take 75mg qd of placebo

Group A2: Placebo, QD

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged 18 to 75 years
• Documentation of a VM diagnosis according to the Barany Society/ ICHD-31
• More than 4 definite dizzy days per month in the 3 months prior to screen
• ≥1 prior preventive treatment failure
• E-diary compliance ≥ 80% during observational phase

You may not qualify if:

• Vestibular hypofunction (unilateral or bilateral)
• History of ear surgery (other than ear tubes)
• Other vestibular diagnoses (excluding treated benign paroxysmal positional vertigo (BPPV)), including Meniere's disease, superior semicircular canal dehiscence syndrome, vestibular neuritis, persistent postural-perceptual dizziness, unilateral or bilateral vestibular hypofunction, cerebellar or brainstem disorders, multiple sclerosis, or motion sickness.
• Prior or current treatment with a CGRP medication
• Individuals are allergic to rimegepant sulfate oral disintegrating tablets or any excipients of rimegepant sulfate oral disintegrating tablets.
• Pregnant women, breastfeeding women, or those unwilling to use approved contraceptive methods during the study participation
• History of serious medical or psychiatric disease, at the discretion of the treating physician (including significant coronary artery disease, peripheral vascular disease, cerebrovascular disease, kidney disease, liver disease, and uncontrolled psychiatric disease or past psychiatric hospitalization)
• A history of severe medical or psychiatric conditions (including significant coronary artery disease, peripheral vascular disease, cerebrovascular disease, renal disease, liver disease, Raynaud's disease, uncontrolled psychiatric disorders, or previous psychiatric hospitalizations) as determined by the treating physician
• A history of mania, psychosis, or suicidal ideation
• A history of drug or alcohol abuse within the 12 months prior to screening, based on the subject's medical records or self-report
• Individuals who have received head, face, or neck botulinum toxin injections (such as Dysport®, Botox®, Xeomin®, Myobloc®, and JeuveauTM) within 4 months before screening or are scheduled for such injections during the study period
• Unwilling to use approved form of birth control during the study
• Ok if on up to 2 migraine prophylactic medications (prescribed for that purpose), dose must be stable for 2 months prior to study start

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (1)

Department of Neurology, The Second Affiliated Hospital, Zhejiang University School of Medicine, No.88 Jiefang Road

Hangzhou, Zhejiang, 310000, China

Location

Related Publications (9)

• Croop R, Goadsby PJ, Stock DA, Conway CM, Forshaw M, Stock EG, Coric V, Lipton RB. Efficacy, safety, and tolerability of rimegepant orally disintegrating tablet for the acute treatment of migraine: a randomised, phase 3, double-blind, placebo-controlled trial. Lancet. 2019 Aug 31;394(10200):737-745. doi: 10.1016/S0140-6736(19)31606-X. Epub 2019 Jul 13.

  PMID: 31311674 BACKGROUND

• Yu S, Kim BK, Guo A, Kim MH, Zhang M, Wang Z, Liu J, Moon HS, Tan G, Yang Q, McGrath D, Hanna M, Stock DA, Gao Y, Croop R, Lu Z. Safety and efficacy of rimegepant orally disintegrating tablet for the acute treatment of migraine in China and South Korea: a phase 3, double-blind, randomised, placebo-controlled trial. Lancet Neurol. 2023 Jun;22(6):476-484. doi: 10.1016/S1474-4422(23)00126-6.

  PMID: 37210098 BACKGROUND

• Sharon JD, Krauter R, Chae R, Gardi A, Hum M, Allen I, Levin M. A placebo controlled, randomized clinical trial of galcanezumab for vestibular migraine: The INVESTMENT study. Headache. 2024 Nov-Dec;64(10):1264-1272. doi: 10.1111/head.14835. Epub 2024 Sep 30.

  PMID: 39344988 BACKGROUND

• Russo CV, Sacca F, Braca S, Sansone M, Miele A, Stornaiuolo A, De Simone R. Anti-calcitonin gene-related peptide monoclonal antibodies for the treatment of vestibular migraine: A prospective observational cohort study. Cephalalgia. 2023 Apr;43(4):3331024231161809. doi: 10.1177/03331024231161809.

  PMID: 36946234 BACKGROUND

• Webster KE, Dor A, Galbraith K, Haj Kassem L, Harrington-Benton NA, Judd O, Kaski D, Maarsingh OR, MacKeith S, Ray J, Van Vugt VA, Burton MJ. Pharmacological interventions for acute attacks of vestibular migraine. Cochrane Database Syst Rev. 2023 Apr 12;4(4):CD015322. doi: 10.1002/14651858.CD015322.pub2.

  PMID: 37042545 BACKGROUND

• Webster K, Dor A, Galbraith K, Kassem LH, Harrington-Benton N, Judd O, Kaski D, Maarsingh O, MacKeith S, Ray J, Van Vugt V, Burton M. Pharmacological interventions for prophylaxis of vestibular migraine. Cochrane Database Syst Rev. 2023 Apr 12;2023(4):CD015187. doi: 10.1002/14651858.CD015187.pub2.

  PMID: 37073858 BACKGROUND

• Cho SJ, Kim BK, Kim BS, Kim JM, Kim SK, Moon HS, Song TJ, Cha MJ, Park KY, Sohn JH. Vestibular migraine in multicenter neurology clinics according to the appendix criteria in the third beta edition of the International Classification of Headache Disorders. Cephalalgia. 2016 Apr;36(5):454-62. doi: 10.1177/0333102415597890. Epub 2015 Jul 29.

  PMID: 26224714 BACKGROUND

• Neuhauser H, Leopold M, von Brevern M, Arnold G, Lempert T. The interrelations of migraine, vertigo, and migrainous vertigo. Neurology. 2001 Feb 27;56(4):436-41. doi: 10.1212/wnl.56.4.436.

  PMID: 11222783 BACKGROUND

• Formeister EJ, Rizk HG, Kohn MA, Sharon JD. The Epidemiology of Vestibular Migraine: A Population-based Survey Study. Otol Neurotol. 2018 Sep;39(8):1037-1044. doi: 10.1097/MAO.0000000000001900.

  PMID: 30020261 BACKGROUND

MeSH Terms

Interventions

rimegepant sulfate

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2025
• First Posted: May 28, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: June 25, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)