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New Trial Tests Migraine Drugs as Potential Tinnitus Treatment

A new clinical trial at Stanford University is directly testing whether newer migraine drugs, designed to block a specific protein, could be more effective for tinnitus than conventional migraine medications. The trial targets a shared biological mechanism between migraine and tinnitus, offering a novel path for treatment.

Approximately 15% of people worldwide experience tinnitus, a persistent ringing or buzzing in the ears with no external source. For those who also have a history of migraine, the sounds can be particularly burdensome. The COMPACT-PM trial seeks to determine which class of migraine preventive medication provides the greatest relief from this intrusive symptom.

A Shared Biological Pathway: The CGRP Connection

The scientific rationale for the trial centers on calcitonin gene-related peptide (CGRP). This protein is a well-established player in migraine pain pathways. It is also active in the inner ear, expressed in cochlear hair cells, the spiral ganglion, and vestibular organs.

Research shows that CGRP levels are elevated in a chronic migraine mouse model and that administering CGRP can reduce cochlear deficits. In humans, some conventional migraine drugs have been observed to lessen tinnitus severity. This evidence points to CGRP as a potential biological link between migraine and tinnitus. The newer anti-CGRP therapies—available as monthly self-injections or oral tablets—work by directly blocking CGRP or its receptor.

“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,” states the trial protocol. COMPACT-PM is designed to fill that gap.

Trial Design and Participant Requirements

This is a randomized, open-label, active-comparator study. A total of 120 adult participants will be enrolled. Like a coin flip, they will be randomly assigned to one of two treatment groups.

Group One will receive conventional migraine preventive therapies. These include antidepressants like amitriptyline, nortriptyline, and venlafaxine; antihypertensives like propranolol, verapamil, and candesartan; and the anticonvulsant topiramate.

Group Two will receive anti-CGRP therapies. These are the newer injectable (e.g., erenumab, fremanezumab, galcanezumab) or oral (e.g., rimegepant, atogepant) agents.

A placebo arm is not included. The researchers note that withholding migraine preventive treatment from patients who clinically need it would be unethical. In both groups, the specific medication is chosen by the treating clinician based on individual patient factors and insurance coverage. All participants must have confirmed insurance access to at least one medication from their assigned class.

To be eligible, participants must be 18 or older with non-pulsatile tinnitus present for at least six months. They must score above 25 on the Tinnitus Functional Index, indicating at least a mild-to-moderate burden. They must also have a physician-diagnosed history of migraine or a related headache disorder and be a candidate for preventive therapy. Other key criteria include a stable medication regimen for the prior three months and the ability to attend in-person study visits at the Stanford Ear Institute.

Measuring Outcomes Beyond the Ringing

The main measure of success is change in the Tinnitus Functional Index score over 24 weeks. The TFI assesses how much tinnitus impacts a person’s life across multiple domains, including concentration, sleep, and emotional state.

The trial will also collect a range of secondary data. This includes standard hearing tests (audiometry), balance assessments, and auditory brainstem response testing to measure neurological function. Participants will keep a comprehensive symptom diary to track headaches and tinnitus severity throughout the study period.

Current Status and Future Implications

The COMPACT-PM trial is currently listed as “NOT_YET_RECRUITING” on ClinicalTrials.gov. It is a Phase 4 trial, meaning it evaluates already-approved medications for a new application (tinnitus treatment). The study is funded by a philanthropic gift to Stanford University’s Department of Otolaryngology – Head & Neck Surgery.

If the anti-CGRP therapies show a stronger effect on reducing tinnitus burden compared to conventional preventives, it would provide a strong rationale for considering these targeted drugs for patients with comorbid migraine and tinnitus. The results could also deepen the understanding of how CGRP influences auditory processing and pave the way for more specific inner-ear treatments.

For the millions of people who navigate the dual challenges of migraine and tinnitus, this trial represents a direct investigation into a treatment strategy that addresses both conditions at their possible biological root.

This article is for informational purposes only. Consult a qualified professional for personalised advice.

Source:
Comparing Migraine Preventive Therapies vs. Anti-CGRP Therapies for Tinnitus in Patients With Migraine (COMPACT-PM) (ClinicalTrials.gov: NCT07655440)