Comparing Migraine Preventive Therapies vs. Anti-CGRP Therapies for Tinnitus in Patients With Migraine (COMPACT-PM) (COMPACT-PM)
15 de junio de 2026 actualizado por: 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.
Descripción general del estudio
Estado
Aún no reclutando
Descripción detallada
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.
Tipo de estudio
Intervencionista
Inscripción (Estimado)
120
Fase
- Fase 4
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Estudio Contacto
- Nombre: Jwala P Rejimon, AuD
- Número de teléfono: 650-736-2354
- Correo electrónico: jrejimon@stanford.edu
Copia de seguridad de contactos de estudio
- Nombre: Research Coordinator
- Correo electrónico: traneric@stanford.edu
Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
No
Descripción
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
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: 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.
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240 mg loading dose, then 120 mg monthly; intramuscular injection.
Manufacturer: Eli Lilly.
70-140 mg monthly; subcutaneous injection.
Manufacturer: Amgen/Novartis.
100-300 mg every 3 months; intravenous infusion.
Manufacturer: Lundbeck.
10, 30, or 60 mg daily; oral.
Manufacturer: AbbVie.
|
|
Comparador activo: 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.
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10-100 mg daily; oral.
Generic.
10-100 mg daily; oral.
Generic.
10-120 mg daily; oral.
Generic.
120-480 mg SR daily; oral.
Generic.
2-32 mg daily; oral. Generic.
12.5-200 mg daily; oral.
Generic.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Change in Tinnitus Functional Index (TFI) Score
Periodo de tiempo: 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
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Change in Tinnitus Functional Index (TFI) Score at 12 Weeks
Periodo de tiempo: 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.
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Baseline to 12 weeks
|
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TFI Score Trajectory
Periodo de tiempo: Weeks 4, 8, 16, 20
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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.
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Weeks 4, 8, 16, 20
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Change in Tinnitus Handicap Inventory (THI) Score
Periodo de tiempo: 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.
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Baseline, 12 weeks, 24 weeks
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Change in Visual Analog Scale (VAS) Tinnitus Loudness
Periodo de tiempo: Baseline, 12 weeks, 24 weeks
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Participant-rated tinnitus loudness on a 0-10 VAS, where 0 = no loudness and 10 = worst imaginable loudness.
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Baseline, 12 weeks, 24 weeks
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Change in Visual Analog Scale (VAS) Tinnitus Unpleasantness
Periodo de tiempo: Baseline, 12 weeks, 24 weeks
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Participant-rated tinnitus unpleasantness on a 0-10 VAS, where 0 = not unpleasant and 10 = worst imaginable unpleasantness.
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Baseline, 12 weeks, 24 weeks
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Patient Global Impression of Change (PGIC)
Periodo de tiempo: 12 weeks, 24 weeks
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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).
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12 weeks, 24 weeks
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Change in Headache Impact Test-6 (HIT-6) Score
Periodo de tiempo: 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.
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Baseline, 12 weeks, 24 weeks
|
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Change in Migraine Disability Assessment (MIDAS) Score
Periodo de tiempo: Baseline, 12 weeks, 24 weeks
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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.
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Baseline, 12 weeks, 24 weeks
|
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Change in Vestibular Migraine Patient Assessment Tool and Handicap Inventory (VM-PATHI) Score
Periodo de tiempo: 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
|
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Change in Dizziness Handicap Inventory (DHI) Score
Periodo de tiempo: 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.
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Baseline, 12 weeks, 24 weeks
|
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Monthly Headache Days
Periodo de tiempo: Baseline through 24 weeks
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Number of headache days per month recorded in participant daily diary, averaged over each 4-week interval between study visits.
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Baseline through 24 weeks
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Monthly Dizzy Days
Periodo de tiempo: Baseline through 24 weeks
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Number of days with dizziness or vertigo per month recorded in participant daily diary, averaged over each 4-week interval between study visits.
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Baseline through 24 weeks
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Monthly Nausea Days
Periodo de tiempo: Baseline through 24 weeks
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Number of days with nausea per month recorded in participant daily diary, averaged over each 4-week interval between study visits.
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Baseline through 24 weeks
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Acute Medication Use
Periodo de tiempo: Baseline through 24 weeks
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Number of days per month with acute migraine or vestibular rescue medication use, recorded in participant daily diary.
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Baseline through 24 weeks
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Change in Pure Tone Audiometric Thresholds
Periodo de tiempo: Baseline, 12 weeks, 24 weeks
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Change in air conduction pure tone thresholds at 250-8000 Hz from baseline, assessed by standard audiogram.
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Baseline, 12 weeks, 24 weeks
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Change in Speech-in-Noise Performance (QuickSIN)
Periodo de tiempo: Baseline, 12 weeks, 24 weeks
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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
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Change in Auditory Brainstem Response (ABR)
Periodo de tiempo: Baseline, 12 weeks, 24 weeks
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Change in ABR wave latencies and amplitudes from baseline, reflecting peripheral and central auditory pathway integrity.
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Baseline, 12 weeks, 24 weeks
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Change in Tinnitus Pitch and Loudness Characteristics
Periodo de tiempo: Baseline, 12 weeks, 24 weeks
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Change in psychoacoustic tinnitus pitch match (Hz) and loudness match (dB SL) from baseline.
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Baseline, 12 weeks, 24 weeks
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Change in Video Head Impulse Test (vHIT)
Periodo de tiempo: Baseline, 12 weeks, 24 weeks
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Change in semicircular canal vestibulo-ocular reflex (VOR) gain and saccades from baseline, assessed by vHIT across all six semicircular canals.
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Baseline, 12 weeks, 24 weeks
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Rotary Chair - VOR Gain
Periodo de tiempo: 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.
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Baseline, 12 weeks, 24 weeks
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Change in Cervical and Ocular Vestibular Evoked Myogenic Potentials (cVEMP/oVEMP)
Periodo de tiempo: Baseline, 12 weeks, 24 weeks
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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
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VNG - Ocular Motor Testing
Periodo de tiempo: 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.
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Baseline, 12 weeks, 24 weeks
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Adverse Event Rate
Periodo de tiempo: Baseline through 24 weeks plus 30-day safety follow-up
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Frequency and severity of adverse events and serious adverse events in each arm, assessed throughout the study period and graded by CTCAE criteria.
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Baseline through 24 weeks plus 30-day safety follow-up
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TFI Responder Rate
Periodo de tiempo: 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).
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24 weeks
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Rotary Chair - VOR Phase
Periodo de tiempo: Time Frame: Baseline, 12 weeks, 24 weeks
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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.
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Time Frame: Baseline, 12 weeks, 24 weeks
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Rotary Chair - VOR Symmetry
Periodo de tiempo: Time Frame: Baseline, 12 weeks, 24 weeks
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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.
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Time Frame: Baseline, 12 weeks, 24 weeks
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VNG - Positional and Positioning Nystagmus
Periodo de tiempo: 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.
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Time Frame: Baseline, 12 weeks, 24 weeks
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VNG - Caloric Testing
Periodo de tiempo: Time Frame: Baseline, 12 weeks, 24 weeks
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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
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Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Change in Hyperacusis Questionnaire (HQ) Score
Periodo de tiempo: 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
|
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Pupillometry Changes
Periodo de tiempo: 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
|
Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Investigadores
- Investigador principal: Kristen K. Steenerson, Stanford University
- Investigador principal: Matthew Fitzgerald, Stanford University
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Estimado)
1 de julio de 2026
Finalización primaria (Estimado)
1 de julio de 2031
Finalización del estudio (Estimado)
1 de julio de 2031
Fechas de registro del estudio
Enviado por primera vez
29 de mayo de 2026
Primero enviado que cumplió con los criterios de control de calidad
15 de junio de 2026
Publicado por primera vez (Actual)
17 de junio de 2026
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
17 de junio de 2026
Última actualización enviada que cumplió con los criterios de control de calidad
15 de junio de 2026
Última verificación
1 de junio de 2026
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Manifestaciones neurológicas
- Enfermedades Cerebrales
- Enfermedades del Sistema Nervioso Central
- Enfermedades del Sistema Nervioso
- Trastornos de cefalea primaria
- Trastornos de dolor de cabeza
- Enfermedades Otorrinolaringológicas
- Trastornos sensoriales
- Enfermedades del oído
- Trastornos de la audición
- Condiciones Patológicas, Signos y Síntomas
- Signos y síntomas
- Trastornos de migraña
- Tinnitus
- Químicos orgánicos
- Hidrocarburos
- Hidrocarburos, cíclico
- Carbohidratos
- Naftalenos
- Hidrocarburos aromáticos policíclicos
- Hidrocarburos, aromáticos
- Compuestos policíclicos
- Amina
- Alcoholes
- Fenoxipropanolaminas
- Propanolaminas
- Amino alcoholes
- Propanols
- Fenetilaminas
- Etilaminas
- Azúcar
- Dibenzocycloheptenes
- Benzocicloheptenos
- Hexisos
- Monosacáridos
- Fructosa
- Cetosis
- Topiramato
- Verapamilo
- Propranolol
- Amitriptilina
- Nortriptilina
- ePtinezumab
- atogepant
- erenumab
- galcanezumab
- candesartán
Otros números de identificación del estudio
- IRB Protocol #86437
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
INDECISO
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Sí
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
No
producto fabricado y exportado desde los EE. UU.
Sí
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .