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

NCT07655440 | Not Yet Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: IRB Protocol #86437
• Study Type: interventional
• Target: 120
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Migraine Associated Vertigo; Tinnitus; Migraine; Vestibular Migraine

Keywords

tinnitus; migraine; vestibular migraine; migraine-associated tinnitus; CGRP

Outcome Measures

Primary Outcomes (1)

• Change in Tinnitus Functional Index (TFI) Score

  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

Secondary Outcomes (28)

• Change in Tinnitus Functional Index (TFI) Score at 12 Weeks

  Baseline to 12 weeks

• TFI Score Trajectory

  Weeks 4, 8, 16, 20

• Change in Tinnitus Handicap Inventory (THI) Score

  Baseline, 12 weeks, 24 weeks

• Change in Visual Analog Scale (VAS) Tinnitus Loudness

  Baseline, 12 weeks, 24 weeks

• Change in Visual Analog Scale (VAS) Tinnitus Unpleasantness

  Baseline, 12 weeks, 24 weeks

Other Outcomes (2)

• Change in Hyperacusis Questionnaire (HQ) Score

  Baseline, 12 weeks, 24 weeks

• Pupillometry Changes

  Baseline, 12 weeks, 24 weeks

Study Arms (2)

CGRP-Targeting Therapy

EXPERIMENTAL

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.

Drug: Galcanezumab; Drug: Erenumab 70 mg; Drug: Eptinezumab; Drug: Atogepant

Conventional Migraine Preventive Therapy

ACTIVE COMPARATOR

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.

Drug: Amitriptyline; Drug: Nortriptyline; Drug: propranolol; Drug: Verapamil SR 120 mg; Drug: Candesartan; Drug: topiramate

Interventions

Galcanezumab DRUG

240 mg loading dose, then 120 mg monthly; intramuscular injection. Manufacturer: Eli Lilly.

CGRP-Targeting Therapy

Erenumab 70 mg DRUG

70-140 mg monthly; subcutaneous injection. Manufacturer: Amgen/Novartis.

CGRP-Targeting Therapy

Eptinezumab DRUG

100-300 mg every 3 months; intravenous infusion. Manufacturer: Lundbeck.

CGRP-Targeting Therapy

Atogepant DRUG

10, 30, or 60 mg daily; oral. Manufacturer: AbbVie.

CGRP-Targeting Therapy

Amitriptyline DRUG

10-100 mg daily; oral. Generic.

Conventional Migraine Preventive Therapy

Nortriptyline DRUG

10-100 mg daily; oral. Generic.

Conventional Migraine Preventive Therapy

propranolol DRUG

10-120 mg daily; oral. Generic.

Conventional Migraine Preventive Therapy

Verapamil SR 120 mg DRUG

120-480 mg SR daily; oral. Generic.

Conventional Migraine Preventive Therapy

Candesartan DRUG

2-32 mg daily; oral. Generic.

Conventional Migraine Preventive Therapy

topiramate DRUG

12.5-200 mg daily; oral. Generic.

Conventional Migraine Preventive Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Stanford University: lead

MeSH Terms

Conditions

Tinnitus; Migraine Disorders

Interventions

galcanezumab; erenumab; eptinezumab; atogepant; Amitriptyline; Nortriptyline; Propranolol; Verapamil; candesartan; Topiramate

Condition Hierarchy (Ancestors)

Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Dibenzocycloheptenes; Benzocycloheptenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Propanols; Amines; Naphthalenes; Phenethylamines; Ethylamines; Fructose; Hexoses; Monosaccharides; Sugars; Carbohydrates; Ketoses

Study Officials

• Kristen K. Steenerson

  Stanford University

  PRINCIPAL INVESTIGATOR

• Matthew Fitzgerald

  Stanford University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jwala P Rejimon, AuD

CONTACT

650-736-2354; jrejimon@stanford.edu

Research Coordinator

CONTACT

traneric@stanford.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Associate Professor

Model Details: Participants are randomized 1:1 to one of two parallel arms: a CGRP-targeting agent arm or a conventional migraine preventive arm. Within each arm, the specific medication is selected by the treating clinician based on clinical appropriateness and patient factors. The conventional arm is organized by pharmacological class: antidepressants (amitriptyline, nortriptyline, venlafaxine), antihypertensives (propranolol, verapamil, candesartan), and anticonvulsants (topiramate).

Study Record Dates

• First Submitted: May 29, 2026
• First Posted: June 17, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2031
• Study Completion (Estimated): July 1, 2031
• Last Updated: June 17, 2026

Record last verified: 2026-06