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

The TFI is a validated 25-item self-report questionnaire measuring the negative impact of tinnitus on daily life. Scores range from 0-100; higher scores indicate greater tinnitus burden. The minimally important clinical difference is 13 points. The primary endpoint is the between-arm difference in TFI change from baseline to 24 weeks. The Tinnitus Functional Index (TFI) is a validated 25-item self-report questionnaire measuring the negative impact of tinnitus on daily life. Scores range from 0-100; higher scores indicate greater tinnitus burden. The minimally important clinical difference is 13 points. The primary endpoint is the between-arm difference in TFI change from baseline to 24 weeks, with a greater reduction indicating better outcome.

Between-arm difference in TFI change from baseline to 12 weeks, to characterize early treatment response. The Tinnitus Functional Index (TFI) is a validated 25-item self-report questionnaire measuring the negative impact of tinnitus on daily life. Scores range from 0-100; higher scores indicate greater tinnitus burden. The minimally important clinical difference is 13 points. The primary endpoint is the between-arm difference in TFI change from baseline to 24 weeks, with a greater reduction indicating better outcome.

Within- and between-arm TFI change at weeks 4, 8, 16, and 20 to characterize the time course of tinnitus response. The Tinnitus Functional Index (TFI) is a validated 25-item self-report questionnaire measuring the negative impact of tinnitus on daily life. Scores range from 0-100; higher scores indicate greater tinnitus burden. The minimally important clinical difference is 13 points. The primary endpoint is the between-arm difference in TFI change from baseline to 24 weeks, with a greater reduction indicating better outcome.

The THI is a validated 25-item questionnaire measuring tinnitus-related handicap across functional, emotional, and catastrophic subscales. Scores range from 0-100. The Tinnitus Handicap Inventory (THI) is a validated 25-item questionnaire measuring tinnitus-related handicap across functional, emotional, and catastrophic subscales. Scores range from 0-100; higher scores indicate greater handicap and worse outcome.

Participant-rated tinnitus loudness on a 0-10 VAS, where 0 = no loudness and 10 = worst imaginable loudness.

Participant-rated tinnitus unpleasantness on a 0-10 VAS, where 0 = not unpleasant and 10 = worst imaginable unpleasantness.

Single-item participant-rated global impression of change in tinnitus since starting study treatment, rated on a 7-point scale from 1 (very much worse) to 7 (very much improved).

The HIT-6 is a validated 6-item questionnaire measuring the impact of headaches on daily functioning. Scores range from 36-78; higher scores indicate greater headache impact.

The Migraine Disability Assessment (MIDAS) quantifies headache-related disability over the prior 3 months based on lost productive time, scored in days. Scores range from 0 to unlimited; higher scores indicate greater disability and worse outcome.

The Vestibular Migraine Patient Assessment Tool and Handicap Inventory (VM-PATHI) is a validated 25-item patient-reported outcome measure specific to vestibular migraine, assessing symptom frequency, severity, and impact. Scores range from 0-100; higher scores indicate greater disease burden and worse outcome. Administered to all participants; subgroup analysis planned for those with confirmed vestibular migraine diagnosis.

The Dizziness Handicap Inventory (DHI) is a validated 25-item questionnaire measuring the self-perceived handicap imposed by dizziness and unsteadiness. Scores range from 0-100; higher scores indicate greater handicap and worse outcome.

Number of headache days per month recorded in participant daily diary, averaged over each 4-week interval between study visits.

Number of days with dizziness or vertigo per month recorded in participant daily diary, averaged over each 4-week interval between study visits.

Number of days with nausea per month recorded in participant daily diary, averaged over each 4-week interval between study visits.

Number of days per month with acute migraine or vestibular rescue medication use, recorded in participant daily diary.

Change in air conduction pure tone thresholds at 250-8000 Hz from baseline, assessed by standard audiogram.

Change in signal-to-noise ratio loss from baseline as measured by the Quick Speech-in-Noise (QuickSIN) test, reflecting auditory processing in noise.

Change in ABR wave latencies and amplitudes from baseline, reflecting peripheral and central auditory pathway integrity.

Change in psychoacoustic tinnitus pitch match (Hz) and loudness match (dB SL) from baseline.

Change in semicircular canal vestibulo-ocular reflex (VOR) gain and saccades from baseline, assessed by vHIT across all six semicircular canals.

Change in vestibulo-ocular reflex (VOR) gain from baseline, assessed by sinusoidal harmonic acceleration rotary chair testing across multiple frequencies. Gain is a unitless ratio (eye velocity / chair velocity); values closer to 1.0 indicate better vestibular function.

Change in cVEMP and oVEMP amplitude, threshold, and latency from baseline, reflecting saccular, utricular, and inferior/superior vestibular nerve function.

Change in ocular motor parameters from baseline assessed by videonystagmography (VNG), including gaze stability, saccade accuracy and latency, smooth pursuit gain, and optokinetic response gain. Each parameter is reported in its respective unit (degrees/second, milliseconds, or unitless ratio); values will be analyzed individually.

Frequency and severity of adverse events and serious adverse events in each arm, assessed throughout the study period and graded by CTCAE criteria.

Proportion of participants in each arm achieving a clinically meaningful reduction of 13 or more points from baseline on the Tinnitus Functional Index (TFI) at 24 weeks, representing the minimum important clinical difference established by Meikle et al. (2012).

Change in vestibulo-ocular reflex (VOR) phase lead from baseline, assessed by sinusoidal harmonic acceleration rotary chair testing. Phase is reported in degrees; lower phase lead at low frequencies indicates better vestibular compensation.

Change in vestibulo-ocular reflex (VOR) directional preponderance/symmetry from baseline, assessed by sinusoidal harmonic acceleration rotary chair testing. Symmetry is reported as a percentage asymmetry; values closer to 0% indicate better symmetry.

Change in nystagmus slow-phase velocity (SPV) from baseline during positional and positioning maneuvers assessed by videonystagmography (VNG). SPV is reported in degrees/second; lower values indicate less nystagmus.

Change in unilateral weakness and directional preponderance from baseline assessed by caloric irrigation during videonystagmography (VNG). Unilateral weakness and directional preponderance are reported as percentages; values closer to 0% indicate better symmetry.

The Hyperacusis Questionnaire (HQ) is a 14-item questionnaire measuring hyperacusis severity and impact. Scores range from 0-42; higher scores indicate greater hyperacusis severity and worse outcome. Included as an exploratory outcome given the frequent co-occurrence of hyperacusis and tinnitus in this population.

Change in sound-evoked pupil dilation amplitude and latency from baseline, as a measure of olivocochlear and autonomic auditory pathway function. Change in resting pupil diameter from baseline as a measure of baseline autonomic tone.

Exploratory mechanistic outcome.