Migraine Medications for Tinnitus

Overseen By Hamid R Djalilian, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of California, Irvine

Disqualifiers: Pregnancy, Adverse reactions, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether certain migraine medications can help people with tinnitus, a condition characterized by ringing or buzzing in the ears. The study examines two medication combinations: Nortriptyline with Topiramate and Verapamil with Paroxetine, to determine if they can lessen tinnitus's impact on daily life. Individuals with moderate to severe tinnitus who can adhere to the medication plan might be suitable for this trial. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, providing an opportunity to understand its benefits for more patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What is the safety track record for these treatments?

Research has shown that combining nortriptyline with topiramate or verapamil with paroxetine can be safe for people with tinnitus. Studies have found that these combinations reduce tinnitus symptoms in about 40% of patients, with fewer side effects at moderate doses.

Nortriptyline, often used for depression, can be increased slowly to minimize side effects. Topiramate, typically used to prevent migraines and seizures, has been safely used for other conditions. However, like any treatment, they may have some side effects.

Verapamil and paroxetine are also commonly used for other health issues. Verapamil is often prescribed for heart conditions, while paroxetine is an antidepressant. Like the first combination, these medications are generally safe at moderate doses.

While more research is needed to confirm long-term safety, current evidence suggests these treatments are generally well-tolerated for tinnitus. Always consult a healthcare provider to understand potential risks based on personal health needs. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for tinnitus because they're exploring a fresh approach by using migraine medications. Unlike traditional tinnitus treatments that often focus on sound therapy or hearing aids, these combinations—Nortriptyline with Topiramate and Verapamil with Paroxetine—target the neurological pathways that might be involved in both migraines and tinnitus. This could offer a dual benefit, addressing underlying neurological issues with a single pill. Such innovative combinations could provide relief for patients for whom standard treatments have been ineffective, potentially transforming the way tinnitus is managed.

What evidence suggests that this trial's treatments could be effective for tinnitus?

This trial will evaluate the effectiveness of two different medication combinations for tinnitus. Research has shown that combining nortriptyline with topiramate, which participants in one arm of this trial may receive, or verapamil with paroxetine, which participants in another arm may receive, can reduce the severity of tinnitus. Studies found that these combinations effectively lessen symptoms in about 40% to 50% of patients. These treatments have fewer side effects at moderate doses and can also help with stress, depression, and anxiety linked to tinnitus. Specifically, patients taking these medications experienced a significant reduction in tinnitus severity compared to those taking a placebo. Overall, evidence suggests that these migraine medications could help manage tinnitus symptoms. ^{1 2 3 4 6}

Who Is on the Research Team?

Hamid R Djalilian, MD

Principal Investigator

Univeristy of California, Irvine

Are You a Good Fit for This Trial?

This trial is for adults aged 25-85 with moderate to severe tinnitus. Participants must be able to read and write English, attend study visits, and comply with medication regimens. Pregnant individuals, those with adverse reactions to the medications being tested or certain medical conditions are excluded.

Inclusion Criteria

Subject must be compliant with the medication and attend study visits.

Must be able to read and write in the English language to provide consenting.

You have moderate to severe ringing in your ears.

Exclusion Criteria

Pregnancy will result in automatic exclusion from the study. Rule out of pregnancy will be done by a urine pregnancy test to confirm the situation for all women who are of child bearing potential

You had a bad reaction to the medication before.

Subject suffers from a medical condition or has history that may be concerning to the investigators clinical opinion

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either nortriptyline plus topiramate, verapamil plus paroxetine, or placebo for 8 weeks. Dosages may be increased weekly based on symptoms.

8 weeks

Weekly visits (in-person or virtual) for symptom monitoring and dosage adjustments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nortriptyline + Topiramate
• Placebo
• Verapamil + Paroxetine

Trial Overview The trial tests if migraine medications can help treat tinnitus. It compares the effectiveness of Nortriptyline plus Topiramate versus Verapamil plus Paroxetine against a placebo in reducing the impact of tinnitus on daily life.

How Is the Trial Designed?

Group I: Verapamil + paroxetine Experimental Treatment 1 Intervention

Verapamil (30 mg) plus paroxetine (4 mg) in a single pill initially taken once daily. Dose may be increased as directed by care provider by 30mg weekly (to a maximum of 240mg) for verapamil, and by 4mg weekly (maximum 32mg) for paroxetine.

Group II: Nortriptyline + topiramate Experimental Treatment 1 Intervention

Nortriptyline (7.5 mg) plus topiramate (10 mg) in a single pill initially taken once daily. Dose may be increased as directed by care provider by 7.5mg weekly (to a maximum of 60mg) for nortriptyline, and by 10mg weekly (maximum 80mg) for topiramate.

Group III: Placebo Placebo Group 1 Intervention

Placebo pill.

Who Is Running the Clinical Trial?

University of California, Irvine

Lead Sponsor

Trials

580

Recruited

4,943,000+

Published Research Related to This Trial

Preventive therapy for migraines is recommended for adults experiencing more than 6 headache days per month, with options including FDA-approved medications like propranolol, topiramate, and onabotulinumtoxinA, as well as effective off-label drugs such as lisinopril and amitriptyline.

The response to preventive treatments varies widely among individuals, with complete cessation of headaches being rare, but some patients experience significant relief, highlighting the importance of personalized treatment plans and gradual dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacologic Prevention of Migraine: A Narrative Review of the State of the Art in 2018. Loder, E., Rizzoli, P.[2019]

Divalproex sodium, the only FDA-approved antiepileptic drug for migraine prevention, significantly reduced migraine frequency by 30% to 40% in patients over 12 weeks, with nearly half of the patients experiencing a 50% or more reduction in headache frequency.

Gabapentin also showed significant efficacy in reducing migraine frequency, with nearly half of patients at higher doses achieving a 50% or more reduction, while topiramate demonstrated effectiveness in reducing migraine frequency in two separate trials, with some patients even experiencing weight loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiepileptic drugs in migraine prevention. Mathew, NT.[2019]

Preventive pharmacological treatments for migraines, such as amitriptyline, divalproex, topiramate, and beta-adrenergic blockers (like propranolol), have strong evidence supporting their efficacy, based on clinical experience and level I evidence.

While these medications can be effective, they also come with varying degrees of side effects that may limit their use, highlighting the importance of balancing treatment efficacy with safety and patient preferences in migraine management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prophylactic pharmacotherapy for migraine headaches. Buchanan, TM., Ramadan, NM.[2006]

Antidepressants, particularly tricyclics, can be beneficial in treating both migraine and depression, but often a single antidepressant is not enough to effectively manage both conditions, necessitating combination therapies.

The review highlights the importance of understanding the interactions between various medications, including antidepressants and migraine prophylactics, to ensure effective treatment while minimizing the risk of adverse interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antidepressants in long-term migraine prevention. Koch, HJ., Jürgens, TP.[2018]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39588680/?utm_source=FeedFetcher&utm_medium=rss&utm_campaign=None&utm_content=0ta0Q3IXt1voohclJGj-6RlAP-94WkWif6eMSAAYb_D&fc=None&ff=20241127232155&v=2.18.0.post9+e462414

Efficacy of Nortriptyline-Topiramate and Verapamil-Paroxetine ... Conclusion: Both combinations of drugs were promising in improving tinnitus severity. However, larger-scale trials with longer follow-up periods ...

2. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/lary.32338?af=R

Optimal Dosing of Nortriptyline–Topiramate and Verapamil ... Both NT and VP combinations at moderate doses effectively reduce tinnitus severity in approximately 40% of patients, with fewer adverse effects ...

3. escholarship.org escholarship.org/content/qt5tm6633k/qt5tm6633k.pdf

Efficacy of Nortriptyline‐Topiramate and Verapamil‐ ... Objective. To evaluate the efficacy of 2 drug combinations on tinnitus severity and associated stress, depression, sleep, and anxiety. Study ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04404439

Treatment of Tinnitus With Migraine Medications Nortriptyline may be increased by 7.5mg weekly (to a maximum of 60mg), topiramate by 10mg weekly (maximum 80mg), verapamil by 30mg weekly (maximum 240mg), and ...

5. medschool.uci.edu medschool.uci.edu/news/neurotology-faculty-pioneers-placebo-controlled-trial-tinnitus

Neurotology Faculty Pioneers Placebo-controlled Trial For ... Both drug combinations resulted in a significant decrease in tinnitus severity captured by the TFI scores, which was not observed in the placebo ...

6. clinicaltrial.be clinicaltrial.be/en/details/188012?per_page=20&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Treatment of Tinnitus With Migraine Medications - Clinica... This study is 8 weeks in duration. There are three arms in the experiment: the first is nortriptyline (7.5 mg) plus topiramate (10 mg), ...