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

15. juni 2026 opdateret af: Kristen K. Steenerson, MD, Stanford University

Comparative Outcomes of Migraine Preventives and Anti-CGRP Therapies for Tinnitus in Patients With Migraine: A Randomized Active-Comparator Controlled Trial (COMPACT-PM)

Many people with migraine also experience tinnitus - a persistent ringing, buzzing, or hissing in the ears - and research suggests these conditions share underlying biological mechanisms, including a protein called calcitonin gene-related peptide (CGRP) that is active in both the brain and the inner ear. COMPACT-PM is a randomized trial comparing two classes of migraine preventive medications in adults with bothersome tinnitus and a history of migraine: anti-CGRP therapies (newer injectable or oral agents that block CGRP or its receptor) versus conventional migraine preventives (antidepressants including amitriptyline, nortriptyline, and venlafaxine; antihypertensives including propranolol, verapamil, and candesartan; and the anticonvulsant topiramate). Participants are randomly assigned - like a coin flip - to one of the two treatment groups; neither group receives a placebo, as both receive active migraine treatment. The study's primary outcome is change in the Tinnitus Functional Index (TFI) over 24 weeks, with additional measures including hearing tests, balance assessments, auditory brainstem response testing, and a comprehensive symptom diary. The study is conducted at the Stanford Ear Institute and is funded by a philanthropic gift to the Department of Otolaryngology - Head & Neck Surgery at Stanford University.

Studieoversigt

Status

Ikke rekrutterer endnu

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

Tinnitus affects approximately 15% of the global population, and migraine history is an established risk factor for both its prevalence and severity. Converging preclinical and clinical evidence implicates calcitonin gene-related peptide (CGRP) signaling at the intersection of these two conditions: CGRP and its receptors are expressed in cochlear inner and outer hair cells, the spiral ganglion, and the vestibular end organs; in a chronic migraine mouse model, cochlear CGRP expression is upregulated and CGRP administration attenuates cochlear deficits; and in humans, conventional migraine preventive 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 a randomized controlled trial.

COMPACT-PM addresses this gap using a randomized, open-label, active-comparator controlled design. A placebo arm is not included because withholding migraine preventive treatment from patients with a clinical indication for preventive therapy would be ethically inappropriate; both arms therefore receive active, clinically indicated migraine treatment, and randomization controls for treatment selection bias. Within each arm, the specific agent is selected by the treating clinician based on clinical appropriateness, patient factors, and insurance coverage; participants must have confirmed insurance access to at least one CGRP-targeting agent prior to randomization.

Undersøgelsestype

Interventionel

Tilmelding (Anslået)

120

Fase

  • Fase 4

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiekontakt

Undersøgelse Kontakt Backup

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

  • Voksen
  • Ældre voksen

Tager imod sunde frivillige

Ingen

Beskrivelse

Inclusion Criteria:

  • Age 18 years or older
  • Non-pulsatile, subjective tinnitus present for at least 6 months
  • Tinnitus Functional Index (TFI) score greater than 25 at screening, indicating at least mild-to-moderate tinnitus burden
  • Current or past history of migraine, vestibular migraine, or episodic headache disorder, diagnosed by a physician or meeting ICHD-3 criteria
  • Clinically appropriate candidate for migraine preventive therapy as determined by the treating clinician
  • Stable medication regimen for at least 3 months prior to enrollment (no new medications started or stopped within 3 months of screening)
  • Ability to provide written informed consent
  • Ability to complete self-report questionnaires in English or with certified interpreter assistance
  • Willingness to attend three in-person study visits over 24 weeks and complete daily symptom diaries

Exclusion Criteria:

  • Pulsatile tinnitus or objective tinnitus (tinnitus audible to examiner)
  • Pregnancy, planned pregnancy during the study period, or breastfeeding
  • Participation in any other interventional tinnitus treatment research protocol during the study period
  • Currently receiving a CGRP-targeting medication (for participants being considered for the conventional arm) or a conventional migraine preventive medication listed in this protocol (for participants being considered for the CGRP arm) - to avoid within-arm ineligibility at randomization
  • Known contraindication to all medications within the assigned study arm
  • History of serious cardiovascular event (myocardial infarction, stroke, or unstable angina) within 6 months of enrollment
  • Severe hepatic or renal impairment that would contraindicate study medications
  • Active psychiatric disorder requiring medication adjustment within 3 months of enrollment
  • Known hypersensitivity or prior serious adverse reaction to a medication within the assigned study arm
  • Active malignancy or life expectancy less than 12 months
  • Inability to complete study procedures or follow-up visits in the judgment of the investigator

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: CGRP-Targeting Therapy
Participants assigned to this arm receive one CGRP-targeting migraine preventive agent selected by the treating clinician based on clinical appropriateness and patient factors. Options include anti-CGRP monoclonal antibodies (galcanezumab, erenumab, fremanezumab, eptinezumab) or gepants (atogepant, rimegepant). Treatment duration is 24 weeks.
Medicin: Galcanezumab
240 mg loading dose, then 120 mg monthly; intramuscular injection. Manufacturer: Eli Lilly.
Medicin: Erenumab 70 mg
70-140 mg monthly; subcutaneous injection. Manufacturer: Amgen/Novartis.
Medicin: Eptinezumab
100-300 mg every 3 months; intravenous infusion. Manufacturer: Lundbeck.
Medicin: Atogepant
10, 30, or 60 mg daily; oral. Manufacturer: AbbVie.
Aktiv komparator: Conventional Migraine Preventive Therapy
Participants assigned to this arm receive one conventional migraine preventive agent selected by the treating clinician based on clinical appropriateness and patient factors. Options are organized by class: antidepressants (amitriptyline, nortriptyline, venlafaxine), antihypertensives (propranolol, verapamil, candesartan), or anticonvulsants (topiramate). Treatment duration is 24 weeks.
Medicin: Amitriptyline
10-100 mg daily; oral. Generic.
Medicin: Nortriptyline
10-100 mg daily; oral. Generic.
Medicin: propranolol
10-120 mg daily; oral. Generic.
Medicin: Verapamil SR 120 mg
120-480 mg SR daily; oral. Generic.
Medicin: Candesartan
2-32 mg daily; oral. Generic.
Medicin: topiramate
12.5-200 mg daily; oral. Generic.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Change in Tinnitus Functional Index (TFI) Score
Tidsramme: Baseline to 24 weeks
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.
Baseline to 24 weeks

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Change in Tinnitus Functional Index (TFI) Score at 12 Weeks
Tidsramme: Baseline to 12 weeks
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.
Baseline to 12 weeks
TFI Score Trajectory
Tidsramme: Weeks 4, 8, 16, 20
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.
Weeks 4, 8, 16, 20
Change in Tinnitus Handicap Inventory (THI) Score
Tidsramme: Baseline, 12 weeks, 24 weeks
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.
Baseline, 12 weeks, 24 weeks
Change in Visual Analog Scale (VAS) Tinnitus Loudness
Tidsramme: Baseline, 12 weeks, 24 weeks
Participant-rated tinnitus loudness on a 0-10 VAS, where 0 = no loudness and 10 = worst imaginable loudness.
Baseline, 12 weeks, 24 weeks
Change in Visual Analog Scale (VAS) Tinnitus Unpleasantness
Tidsramme: Baseline, 12 weeks, 24 weeks
Participant-rated tinnitus unpleasantness on a 0-10 VAS, where 0 = not unpleasant and 10 = worst imaginable unpleasantness.
Baseline, 12 weeks, 24 weeks
Patient Global Impression of Change (PGIC)
Tidsramme: 12 weeks, 24 weeks
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).
12 weeks, 24 weeks
Change in Headache Impact Test-6 (HIT-6) Score
Tidsramme: Baseline, 12 weeks, 24 weeks
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.
Baseline, 12 weeks, 24 weeks
Change in Migraine Disability Assessment (MIDAS) Score
Tidsramme: Baseline, 12 weeks, 24 weeks
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.
Baseline, 12 weeks, 24 weeks
Change in Vestibular Migraine Patient Assessment Tool and Handicap Inventory (VM-PATHI) Score
Tidsramme: Baseline, 12 weeks, 24 weeks
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.
Baseline, 12 weeks, 24 weeks
Change in Dizziness Handicap Inventory (DHI) Score
Tidsramme: Baseline, 12 weeks, 24 weeks
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.
Baseline, 12 weeks, 24 weeks
Monthly Headache Days
Tidsramme: Baseline through 24 weeks
Number of headache days per month recorded in participant daily diary, averaged over each 4-week interval between study visits.
Baseline through 24 weeks
Monthly Dizzy Days
Tidsramme: Baseline through 24 weeks
Number of days with dizziness or vertigo per month recorded in participant daily diary, averaged over each 4-week interval between study visits.
Baseline through 24 weeks
Monthly Nausea Days
Tidsramme: Baseline through 24 weeks
Number of days with nausea per month recorded in participant daily diary, averaged over each 4-week interval between study visits.
Baseline through 24 weeks
Acute Medication Use
Tidsramme: Baseline through 24 weeks
Number of days per month with acute migraine or vestibular rescue medication use, recorded in participant daily diary.
Baseline through 24 weeks
Change in Pure Tone Audiometric Thresholds
Tidsramme: Baseline, 12 weeks, 24 weeks
Change in air conduction pure tone thresholds at 250-8000 Hz from baseline, assessed by standard audiogram.
Baseline, 12 weeks, 24 weeks
Change in Speech-in-Noise Performance (QuickSIN)
Tidsramme: Baseline, 12 weeks, 24 weeks
Change in signal-to-noise ratio loss from baseline as measured by the Quick Speech-in-Noise (QuickSIN) test, reflecting auditory processing in noise.
Baseline, 12 weeks, 24 weeks
Change in Auditory Brainstem Response (ABR)
Tidsramme: Baseline, 12 weeks, 24 weeks
Change in ABR wave latencies and amplitudes from baseline, reflecting peripheral and central auditory pathway integrity.
Baseline, 12 weeks, 24 weeks
Change in Tinnitus Pitch and Loudness Characteristics
Tidsramme: Baseline, 12 weeks, 24 weeks
Change in psychoacoustic tinnitus pitch match (Hz) and loudness match (dB SL) from baseline.
Baseline, 12 weeks, 24 weeks
Change in Video Head Impulse Test (vHIT)
Tidsramme: Baseline, 12 weeks, 24 weeks
Change in semicircular canal vestibulo-ocular reflex (VOR) gain and saccades from baseline, assessed by vHIT across all six semicircular canals.
Baseline, 12 weeks, 24 weeks
Rotary Chair - VOR Gain
Tidsramme: Baseline, 12 weeks, 24 weeks
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.
Baseline, 12 weeks, 24 weeks
Change in Cervical and Ocular Vestibular Evoked Myogenic Potentials (cVEMP/oVEMP)
Tidsramme: Baseline, 12 weeks, 24 weeks
Change in cVEMP and oVEMP amplitude, threshold, and latency from baseline, reflecting saccular, utricular, and inferior/superior vestibular nerve function.
Baseline, 12 weeks, 24 weeks
VNG - Ocular Motor Testing
Tidsramme: Baseline, 12 weeks, 24 weeks
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.
Baseline, 12 weeks, 24 weeks
Adverse Event Rate
Tidsramme: Baseline through 24 weeks plus 30-day safety follow-up
Frequency and severity of adverse events and serious adverse events in each arm, assessed throughout the study period and graded by CTCAE criteria.
Baseline through 24 weeks plus 30-day safety follow-up
TFI Responder Rate
Tidsramme: 24 weeks
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).
24 weeks
Rotary Chair - VOR Phase
Tidsramme: Time Frame: Baseline, 12 weeks, 24 weeks
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.
Time Frame: Baseline, 12 weeks, 24 weeks
Rotary Chair - VOR Symmetry
Tidsramme: Time Frame: Baseline, 12 weeks, 24 weeks
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.
Time Frame: Baseline, 12 weeks, 24 weeks
VNG - Positional and Positioning Nystagmus
Tidsramme: Time Frame: Baseline, 12 weeks, 24 weeks
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.
Time Frame: Baseline, 12 weeks, 24 weeks
VNG - Caloric Testing
Tidsramme: Time Frame: Baseline, 12 weeks, 24 weeks
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.
Time Frame: Baseline, 12 weeks, 24 weeks

Andre resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Change in Hyperacusis Questionnaire (HQ) Score
Tidsramme: Baseline, 12 weeks, 24 weeks
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.
Baseline, 12 weeks, 24 weeks
Pupillometry Changes
Tidsramme: Baseline, 12 weeks, 24 weeks

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.
Baseline, 12 weeks, 24 weeks

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Stanford University

Efterforskere

  • Ledende efterforsker: Kristen K. Steenerson, Stanford University
  • Ledende efterforsker: Matthew Fitzgerald, Stanford University

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Anslået)

1. juli 2026

Primær færdiggørelse (Anslået)

1. juli 2031

Studieafslutning (Anslået)

1. juli 2031

Datoer for studieregistrering

Først indsendt

29. maj 2026

Først indsendt, der opfyldte QC-kriterier

15. juni 2026

Først opslået (Faktiske)

17. juni 2026

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

17. juni 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

15. juni 2026

Sidst verificeret

1. juni 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • IRB Protocol #86437

Plan for individuelle deltagerdata (IPD)

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Studerer et amerikansk FDA-reguleret enhedsprodukt

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produkt fremstillet i og eksporteret fra U.S.A.

Ja

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