Treatment of Tinnitus With Migraine Medications

NCT04404439 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 20184458
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Tinnitus, Subjective; Tinnitus

Keywords

tinnitus; medication; randomized; trial; migraine; clinical

Outcome Measures

Primary Outcomes (1)

• Tinnitus Functional Index (TFI)

  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 Outcomes (4)

• Patient Health Questionnaire (PHQ)

  Baseline and 8 weeks

• Perceived Stress Scale (PSS)

  Baseline and 8 weeks

• Pittsburgh Sleep Quality Index (SQI)

  Baseline and 8 weeks

• Generalized Anxiety Disorder (GAD-7)

  Baseline and 8 weeks

Study Arms (3)

Nortriptyline + Topiramate

EXPERIMENTAL

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

Verapamil + Paroxetine

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Placebo pill (Microcrystalline Cellulose; PH105) taken once daily. Dose may be increased as directed by care provider.

Drug: Placebo

Interventions

Nortriptyline + Topiramate DRUG

Group NT

Nortriptyline + Topiramate

Verapamil + Paroxetine DRUG

Group VP

Verapamil + Paroxetine

Placebo DRUG

Group P

Placebo

Eligibility Criteria

• Age: 25 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, Irvine: lead
• Otolaryngology Medical Clinic,University of California, Irvine: collaborator

Study Sites (1)

University of California, Irvine Medical Center ENT Clinic (Pavilion 2)

Orange, California, 92868, United States

Location

Related Publications (17)

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  PMID: 9707649 BACKGROUND

MeSH Terms

Conditions

Tinnitus; Migraine Disorders

Interventions

Nortriptyline; Topiramate; Verapamil; Paroxetine

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; Fructose; Hexoses; Monosaccharides; Sugars; Carbohydrates; Ketoses; Phenethylamines; Ethylamines; Amines; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Limitations include selection bias from per-protocol analysis, limited generalizability, short 8-week follow-up, and small sample size, which may reduce power to detect group differences. While excluding nonadherent patients may increase type I error, intention-to-treat analysis supported findings. Despite some high responders, more patients in active groups met the MCID and consistently showed greater, clinically meaningful TFI improvement than placebo.

Results Point of Contact

• Title: Mehdi Abouzari, MD, PhD
• Organization: University of California, Irvine

entclinicalstu@hs.uci.edu

714.456.5753

Study Officials

• Hamid R Djalilian, MD

  Univeristy of California, Irvine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Neurotology and Skull Base Surgery

Study Record Dates

• First Submitted: May 17, 2020
• First Posted: May 27, 2020
• Study Start: September 26, 2019
• Primary Completion: December 30, 2023
• Study Completion: December 30, 2023
• Last Updated: April 16, 2026
• Results First Posted: April 16, 2026

Record last verified: 2026-03

Locations

US (1)