Treatment of Tinnitus With Migraine Medications: A Randomized Clinical Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 78
- 试验地点
- 2
- 主要终点
- Tinnitus Functional Index (TFI)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 25 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Placebo
Placebo pill (Microcrystalline Cellulose; PH105) taken once daily. Dose may be increased as directed by care provider.
干预措施: Placebo (Drug)
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.
干预措施: Nortriptyline + Topiramate (Drug)
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.
干预措施: Verapamil + Paroxetine (Drug)
结局指标
主要结局
Tinnitus Functional Index (TFI)
时间窗: 8 weeks
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.
Tinnitus Functional Index (TFI)
时间窗: 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).
次要结局
- Sleep Quality Index (SQI)(8 weeks)
- Visual Analog Scale (VAS)(8 weeks)
- Patient Health Questionnaire (PHQ)(8 weeks)
- Perceived Stress Scale (PSS)(8 weeks)
- 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)
研究者
Hamid Djalilian
Professor, Neurotology and Skull Base Surgery
University of California, Irvine