Treatment of Tinnitus With Migraine Medications

March 30, 2026 updated by: Hamid Djalilian, University of California, Irvine

Treatment of Tinnitus With Migraine Medications: A Randomized Clinical Trial

Tinnitus represents one of the most common and distressing otologic problems, and it causes various somatic and psychological disorders that interfere with the quality of life. In addition, it contributes significant costs to the healthcare system. However, the mechanisms of tinnitus are poorly understood. and there is currently no FDA-approved medication to treat this condition. Current pharmacological treatment options address the stress, anxiety, and depression that are caused by tinnitus. There is an increased evidence of an epidemiological and mechanistic association between tinnitus and migraine. Therefore, in this study, we intended to evaluate the effectiveness of two combinations of migraine medications on patients with moderate to severe tinnitus by comparing them to placebo.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is an 8-week double-blind, randomized (1:1:1), placebo controlled clinical trial, including adult participants with moderate to severe tinnitus (Tinnitus Functional Index (TFI) >25). After consenting, the participants will be randomized into one of the three arms: the first is nortriptyline (7.5 mg) plus topiramate (10 mg), the second is verapamil (30 mg) plus paroxetine (4 mg), and the third is a placebo group (Microcrystalline Cellulose; PH105). The capsules are in same color and shape and will be supplied by the UCI medical center on-site pharmacy, each containing the initial dosage of medications. All 3 treatments groups might include dose escalation from initial dosage during the study. 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 paroxetine by 4mg weekly (maximum 32mg). Participants will be contacted by a blinded physician via telephone once per week and in-person visits will be scheduled for week 0, 4, and 8. If during these weekly contacts, the participant reports less than 20% improvement in tinnitus compared to the baseline Visual Analog Scale (VAS) obtained at the beginning of the trial, the physician will instruct the participant to increase the dosage for that week. Conversely, if a participant reports more than or equal to 20% improvement as compared to the baseline VAS, the team member will advise the participant to maintain the same dosage of medication for 1 week until the next weekly check-in. Furthermore, at the clinical assessment visits, participants will complete a tablet-based assessment of tinnitus symptoms. The questionnaire results will be securely transferred to a REDCap database. A data safety monitor will address any reported side effects throughout the study.

The within-arm analyses will be based on per-protocol estimand and tested with paired 2-tailed t tests. The between-arm analyses will be based on a per-protocol estimand and tested with analysis of variance (ANOVA) analysis. In addition, an intention-to-treat analysis will be also conducted with identical methods and analyses.

Study Type

Interventional

Enrollment (Actual)

78

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Orange, California, United States, 92868
        • University of California, Irvine Medical Center ENT Clinic (Pavilion 2)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

25 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients with moderate to severe tinnitus.
  • Male or female between the ages of 25 to 85 years.
  • 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.

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.
  • Subject with history of an adverse reaction to medication being prescribed.
  • Subject suffers from a medical condition or has history that may be concerning to the investigators clinical opinion.
  • All contraindications for the medications which prevent subjects from randomization will be considered as exclusion criteria.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Nortriptyline + Topiramate
Nortriptyline (7.5 mg) plus topiramate (10 mg) 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.
Drug: Nortriptyline + Topiramate
Group NT
Experimental: Verapamil + Paroxetine
Verapamil (30 mg) plus paroxetine (4 mg) 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.
Drug: Verapamil + Paroxetine
Group VP
Placebo Comparator: Placebo
Placebo pill (Microcrystalline Cellulose; PH105) taken once daily. Dose may be increased as directed by care provider.
Drug: Placebo
Group P

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tinnitus Functional Index (TFI)
Time Frame: Baseline and 8 weeks (end of trial)
The TFI is a 25 item questionnaire rated on a 0 to 10 scale evaluating the negative impact of tinnitus across 8 domains: Intrusive, Sense of control, Cognitive, Sleep, Auditory, Relaxation, Quality of life, and Emotional. A 0 score indicates low to no impact where a 10 would indicate distress or great impact. The overall TFI score is calculated by dividing the sum of the responses (max possible 250) by the number of responses to get the mean, then multiplying the mean by 10 to obtain the overall TFI score. Overall TFI score can range from 0 to 100. Scores > 31 indicate tinnitus is a moderate to significant problem. A reduction of 13 points in TFI is considered the Minimal Clinically Important Difference (MCID).
Baseline and 8 weeks (end of trial)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Patient Health Questionnaire (PHQ)
Time Frame: Baseline and 8 weeks
Change in depression symptoms based on the Patient Health Questionnaire-9 (PHQ-9), scored from 0 to 27. Higher scores indicate greater symptom severity. A negative change reflects improvement. Mean changes from baseline to Week 8 were analyzed using paired t-tests (per-protocol). A ≥5-point improvement was considered the minimal clinically important difference (MCID).
Baseline and 8 weeks
Perceived Stress Scale (PSS)
Time Frame: Baseline and 8 weeks
Change in perceived stress symptoms based on the Perceived Stress Scale (PSS), scored from 0 to 40. The PSS is a 10 question Likert-type scale with answers ranging from (0) "Never" to (4) "Very often". Four questions with positive statements are scored in reverse (0 = 4, 1 = 3, 2 = 2, 3 = 1, 4 = 0). Higher scores indicate greater stress. A negative change reflects improvement. Mean changes from baseline to Week 8 were analyzed using paired t-tests (per-protocol). A ≥11-point improvement was considered the minimal clinically important difference (MCID).
Baseline and 8 weeks
Pittsburgh Sleep Quality Index (SQI)
Time Frame: Baseline and 8 weeks
Change in sleep quality based on the Pittsburgh Sleep Quality Index (PSQI), scored from 0 to 21. Higher scores indicate poorer sleep quality. A negative change reflects improvement. Mean changes from baseline to Week 8 were analyzed using paired 2-tailed t-tests (per-protocol). Standard error was calculated using end-of-trial SD and sample size. A ≥3-point improvement was considered the minimal clinically important difference (MCID).
Baseline and 8 weeks
Generalized Anxiety Disorder (GAD-7)
Time Frame: Baseline and 8 weeks
Change in anxiety symptoms based on the Generalized Anxiety Disorder-7 (GAD-7) scale, scored from 0 to 21. Higher scores indicate greater anxiety. A negative change reflects improvement. Mean changes from baseline to Week 8 were analyzed using paired 2-tailed t-tests (per-protocol). Standard error was calculated using end-of-trial SD and sample size. A ≥4-point improvement was considered the minimal clinically important difference (MCID).
Baseline and 8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, Irvine

Collaborators

Otolaryngology Medical Clinic,University of California, Irvine

Investigators

  • Principal Investigator: Hamid R Djalilian, MD, Univeristy of California, Irvine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 26, 2019

Primary Completion (Actual)

December 30, 2023

Study Completion (Actual)

December 30, 2023

Study Registration Dates

First Submitted

May 17, 2020

First Submitted That Met QC Criteria

May 21, 2020

First Posted (Actual)

May 27, 2020

Study Record Updates

Last Update Posted (Actual)

April 16, 2026

Last Update Submitted That Met QC Criteria

March 30, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20184458

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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