Treatment of Tinnitus With Migraine Medications

Study Overview
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Brief Summary
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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. It is well-understood that many factors, such as poor education, lower income, or occupational, and recreational activity associated with high noise exposure, influences the prevalence and risk of tinnitus. Although the economic and emotional impact of tinnitus is large, there is currently no FDA-approved medication to treat this condition. However, there are pharmacological options to address the stress, anxiety, and depression that are caused by tinnitus. In this project, we intend to use medications for patients with tinnitus in order to decrease the impact of tinnitus on their daily life and activities.

Detailed Description
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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), the second is verapamil (30 mg) plus paroxetine (4 mg), and the third is a placebo group. This is a double-blinded trial. Participants will be randomized to one arm for the duration of the trial using simple randomization with a computer-generated number. Both medication combinations and placebo may include dosage increases weekly if symptoms do not improve. 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). Symptomatic survey scores from each arm will be obtained before and after treatment and weekly. An unblinded neurotologist attending (Dr. Harrison Lin) will also become involved with patients' treatments as they start to report changes in symptoms in order to monitor their safety and provide advice on change in dosage if patients have questions.

Official Title
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Treatment of Tinnitus With Migraine Medications: A Randomized Clinical Trial

Conditions
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Tinnitus, Subjective, Tinnitus

Intervention / Treatment
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* Drug: Nortriptyline + topiramate
* Drug: Verapamil + paroxetine
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be assigned to a study group by chance (like a coin flip) rather than by a medical decision made by the researchers. There are three arms in the study (treatment group 1 which consists of nortriptyline + topiramate, treatment group 2 which consist of verapamil + paroxetine, and a placebo group), and participants enrolling in the trial will be randomly assigned in a 1:1:1 fashion to one of the arms. The participant will remain in the same arm for the duration of the study (8 weeks). There may be multiple participants in each arm who are undergoing the study at the same time (parallel model).
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nortriptyline + topiramate<br>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. | Drug: Nortriptyline + topiramate<br>* Treatment group 1<br>|
| Experimental: Verapamil + paroxetine<br>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. | Drug: Verapamil + paroxetine<br>* Treatment group 2<br>|
| Placebo Comparator: Placebo<br>Placebo pill. | Other: Placebo<br>* Placebo comparator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tinnitus Functional Index (TFI) | Subjective improvement from baseline in tinnitus symptoms as measured by Tinnitus Functional Index (TFI). The TFI is scored from 0% to 100%, with higher scores indicating a more negative impact of tinnitus. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analog Scale (VAS) | Subjective improvement in tinnitus loudness severity based on a visual analog scale (VAS). The VAS is scored from 0 to 10, with a higher score representing an increased severity of tinnitus. | 8 weeks | 
| Patient Health Questionnaire (PHQ) | Subjective improvement in depression symptoms based on patient health questionnaire (PHQ). The PHQ is scored from 0 to 27, with a higher score indicating increased depression severity. | 8 weeks | 
| Perceived Stress Scale (PSS) | Subjective improvement in stress based on perceived stress scale (PSS). The PSS is scored from 0 to 40, with higher scores indicating higher perceived stress. | 8 weeks | 
| Sleep Quality Index (SQI) | Subjective improvement in sleep quality based on sleep quality index (SQI). The SQI is scored from 0 to 21, with higher scores indicating worse quality of sleep. | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RCT, tinnitus, medication, randomized, trial, migraine