Comparing Migraine Preventive Therapies vs. Anti-CGRP Therapies for Tinnitus in Patients With Migraine (COMPACT-PM)

Tinnitus affects approximately 15% of the global population, and migraine history is anestablished risk factor for both its prevalence and severity. Converging preclinical andclinical evidence implicates calcitonin gene‐related peptide (CGRP) signaling at theintersection of these two conditions: CGRP and its receptors are expressed in cochlearinner and outer hair cells, the spiral ganglion, and the vestibular end organs; in achronic migraine mouse model, cochlear CGRP expression is upregulated and CGRPadministration attenuates cochlear deficits; and in humans, conventional migrainepreventive medications have been shown to reduce tinnitus burden as measured by the TFI.Whether CGRP‐targeting agents confer additional or differential benefit for tinnitus ‐given their direct cochlear and vestibular targets ‐ has not been evaluated in arandomized controlled trial.COMPACT‐PM addresses this gap using a randomized, open‐label, active‐comparatorcontrolled design. A placebo arm is not included because withholding migraine preventivetreatment from patients with a clinical indication for preventive therapy would beethically inappropriate; both arms therefore receive active, clinically indicatedmigraine treatment, and randomization controls for treatment selection bias. Within eacharm, the specific agent is selected by the treating clinician based on clinicalappropriateness, patient factors, and insurance coverage; participants must haveconfirmed insurance access to at least one CGRP‐targeting agent prior to randomization.