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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Galcanezumab
  240 mg loading dose, then 120 mg monthly; intramuscular injection. Manufacturer: Eli Lilly.
• Препарат Erenumab 70 mg
  70-140 mg monthly; subcutaneous injection. Manufacturer: Amgen/Novartis.
• Препарат Eptinezumab
  100-300 mg every 3 months; intravenous infusion. Manufacturer: Lundbeck.
• Препарат Atogepant
  10, 30, or 60 mg daily; oral. Manufacturer: AbbVie.
• Препарат Amitriptyline
  10-100 mg daily; oral. Generic.
• Препарат Nortriptyline
  10-100 mg daily; oral. Generic.
• Препарат propranolol
  10-120 mg daily; oral. Generic.
• Препарат Verapamil SR 120 mg
  120-480 mg SR daily; oral. Generic.
• Препарат Candesartan
  2-32 mg daily; oral. Generic.
• Препарат topiramate
  12.5-200 mg daily; oral. Generic.

Первичные конечные точки

• Change in Tinnitus Functional Index (TFI) Score [Срок оценки: Baseline to 24 weeks]

Вторичные конечные точки (12)

• Change in Tinnitus Functional Index (TFI) Score at 12 Weeks [Срок оценки: Baseline to 12 weeks]
• TFI Score Trajectory [Срок оценки: Weeks 4, 8, 16, 20]
• Change in Tinnitus Handicap Inventory (THI) Score [Срок оценки: Baseline, 12 weeks, 24 weeks]
• Change in Visual Analog Scale (VAS) Tinnitus Loudness [Срок оценки: Baseline, 12 weeks, 24 weeks]
• Change in Visual Analog Scale (VAS) Tinnitus Unpleasantness [Срок оценки: Baseline, 12 weeks, 24 weeks]
• Patient Global Impression of Change (PGIC) [Срок оценки: 12 weeks, 24 weeks]
• Change in Headache Impact Test-6 (HIT-6) Score [Срок оценки: Baseline, 12 weeks, 24 weeks]
• Change in Migraine Disability Assessment (MIDAS) Score [Срок оценки: Baseline, 12 weeks, 24 weeks]
• Change in Vestibular Migraine Patient Assessment Tool and Handicap Inventory (VM-PATHI) Score [Срок оценки: Baseline, 12 weeks, 24 weeks]
• Change in Dizziness Handicap Inventory (DHI) Score [Срок оценки: Baseline, 12 weeks, 24 weeks]
• Monthly Headache Days [Срок оценки: Baseline through 24 weeks]
• Monthly Dizzy Days [Срок оценки: Baseline through 24 weeks]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07655440 · IRB Protocol #86437

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗