xRead - Episodic Vertigo (January 2026)

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15264610, 2024, 10, Downloaded from https://headachejournal.onlinelibrary.wiley.com/doi/10.1111/head.14835 by University Of Michigan Library, Wiley Online Library on [21/10/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License

HEADACHE

treating dizziness. We found that galcanezumab reduced dizziness more than placebo in patients with vestibular migraine.

KEYWORDS dizziness, galcanezumab, vestibular migraine

INTRODUCTION

randomized 1:1 and treated with either galcanezumab or placebo for 3 months. Blocking was used in increments of 10 participants to ensure equitable distribution of participants into the two treatment arms and to allow blocks to be analyzed separately if an early stopping rule was applied. In addition, stratification by sex and VM versus probable VM was used to ensure equal al location. Randomization was achieved with randomization tables that were generated prior to the start of the trial by the study statistician using www.​random.​org. The onsite research phar macist handled stratification and randomization; the investiga tors with participant contact had no access to the randomization tables and never saw them until data lock, ensuring allocation concealment. There were four study visits over 4 months: study visit 1 (SV1) for screening and informed consent (day 0); study visit 2 (SV2) for base line data collection, randomization, and treatment (day 30); study visit 3 (SV3) for continued treatment and monitoring (day 60); and study visit 4 (SV4) for final data collection (day 120). The first treat ment was with a loading dose of two preloaded syringes of 120mg (total dose 240mg) of galcanezumab or placebo, and each subse quent injection was with 120mg of galcanezumab or placebo. Both participants and investigators were blind to the treatment arm. All participants were enrolled by either J.D.S. or R.K., who would alert the research pharmacist prior to SV2, and provide the participant's sex and diagnosis. If the participant then met final eligibility criteria and agreed to proceed, a study coordinator would collect the study medication from the research pharmacist. Two prefilled syringes would be provided at SV2, and then again at SV3. Galcanezumab and placebo (excipients only) were supplied as visually indistinguishable 1 ml, single-dose, prefilled, disposable syringes with study-specific labels. At SV2, both syringes containing 120mg of galcanezumab or placebo were administered, whereas at SV3, one syringe was ad ministered, and the second was given to the participant in a cold pack, with instructions for storage and home administration at day 90. Home administration was confirmed by the study coordinator on day 90, and the empty syringe was returned to the study team during SV4 to ensure compliance. Eligible participants were aged 18 to 75 at the time of screen ing, with a diagnosis of VM or probable VM per Barany Society criteria. 2,15 They had to be fluent in English and have access to a cell phone and email. During the baseline period (SV1-SV2), partic ipants had to have > 4 definitive dizzy days (DDDs) and score > 25 on the VM-PATHI (Vestibular Migraine Patient Assessment Tool and Handicap Inventory). Patients were excluded if they had vestibular hypofunction, a history of ear surgery other than ear tubes, a history

Vestibular migraine (VM) is one of the most common vestibular dis orders, affecting 2.7% of the US population. 1 Diagnostic criteria are available from the Barany Society, recognizing both VM and prob able VM. 2 Clinical features include vertigo, dizziness, headache, motion sensitivity, photophobia, phonophobia, aural pressure, tin nitus, and brain fog. 3–6 No consistent pathophysiologic finding has yet been found; a careful history, physical exam, and audiometry are needed to rule out vestibulopathy that can present similarly, includ ing Meniere's disease, superior canal dehiscence, and persistent pos tural perceptual dizziness. 7 Despite its prevalence, there is a paucity of evidence of VM. This was highlighted in an expert panel review in 2022. 7,8 Two Cochrane Reviews from 2023 found little evidence for the use of abortive or prophylactic medications for VM. 9,10 This included only one placebo-­ controlled randomized clinical trial for prophylaxis, with 95mg of metoprolol. 11 Calcitonin gene–related peptide (CGRP) has been shown to be an excellent target for the treatment of headaches due to mi graine. 12 A prospective observational cohort study found that monoclonal antibodies targeting both the CGRP receptor and CGRP ligand were highly effective for VM, with 90% of partici pants experiencing at least a 50% reduction in vertigo attacks. 12,13 Animal studies also suggest a link between CGRP and vestibulop athy. Rahman et al. found that CGRP infusion worsened balance and increased anxiety in mice. 14 CGRP is expressed in vestib ular organs, and CGRP knockout mice display abnormalities of vestibulo-ocular reflex gain. 15 The INVESTMENT (Investigating Vestibular Migraine Emgality Treatment) trial was designed to assess whether CGRP blockade with galcanezumab is effective in reducing dizziness in VM. We hy pothesized that it would be. To our knowledge, this is the first con trolled trial of CGRP antagonist treatment for VM.

METHODS

The INVESTMENT trial was conducted at a single study site in San Francisco from October 2020 until March 2023 at a tertiary care ves tibular clinic. The study protocol was published on clinic​ altr​ials.​gov (NCT04417361), and research was approved by the University of California, San Francisco Institutional Review Board, reference number 19-29340. Enrolled participants first underwent a base line period without intervention, lasting 1 month. They were then