Tinnitus, Tinnitus, Subjective
Conditions
Keywords
tinnitus, medication, randomized, trial, migraine, clinical
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.
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.
Interventions
Sponsors
University of California, Irvine
Otolaryngology Medical Clinic,University of California, Irvine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
25 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tinnitus Functional Index (TFI) | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient Health Questionnaire (PHQ) | 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). |
| Perceived Stress Scale (PSS) | 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). |
| Pittsburgh Sleep Quality Index (SQI) | 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). |
| Generalized Anxiety Disorder (GAD-7) | 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). |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORHamid R Djalilian, MD
Univeristy of California, Irvine
Participant flow
Recruitment details
The study was conducted at the neurotology clinic of the UC Irvine Medical Center, was approved by the Institutional Review Board, and registered on ClinicalTrials.gov (NCT04404439). After consenting, participants were randomized among 3 parallel arms. participants were contacted by a blinded physician via telephone once per week during the trial and in-person visits were
Pre-assignment details
Participants had to be compliant with the medication regimen and attend study visits. They underwent comprehensive otolaryngologic assessments, including an audiogram, and provided informed consent. In addition, patients underwent a magnetic Exclusion criteria included pregnancy, psychosis, neurological neoplasm, active ear disease affecting hearing, allergies or adverse reactions to study medications, concerning medical conditions like arrhythmia, and any contraindications to the study drugs.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 58.1 Years STANDARD_DEVIATION 14.1 |
| Race and Ethnicity Not Collected | 0 Participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 44 Participants |
| Tinnitus Functional Index (TFI) | 54.7 Score on a Scale STANDARD_DEVIATION 16.7 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 28 | 0 / 27 |
| other Total, other adverse events | 2 / 23 | 6 / 28 | 0 / 27 |
| serious Total, serious adverse events | 0 / 23 | 0 / 28 | 0 / 27 |
Outcome results
None listed