A Study on the Effect of Cilostazol in Patients With Chronic Tinnitus

Study Overview
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Brief Summary
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Overview of tinnitus Tinnitus is a noisy sound which is perceived without any external sound source. According to the survey of the US, 10-20% of adult have the symptom of tinnitus and 3-5% of tinnitus patients have severe discomfort of daily life. Severe tinnitus can result in psychiatric problems such as depression and anxiety disorders. Enhancement of environmental sound, hearing aids, sound generators, cognitive therapy, transcranial magnetic therapy, and drug therapy have been tried for treatment of tinnitus. Nitric oxide(NO) is a well-known neurotransmitter acting as a vasodilator through regulation of production of cyclic guanosine monophosphate(cGMP) and can be found in various sites of cochlea. It is reported that cGMP enhances activity of protein kinase A (PKA), a mediator of platelet aggregation inhibition and vasodilatation and results in increase of vascular flow. Characteristics of the clinical research drug, cilostazol Cilostazol inhibits phosphodiesterase type 3 (PDE3) selectively and increases amount of cAMP by inhibition of degradation of cyclic adenosine monophosphate(cAMP). cAMP again by increasing the active form of PKA suppress the production of blood clots and increase blood flow by expanding blood vessels. Anti-platelet activity and vasodilatation effect of cilostazol have been used for improvement of diabetic peripheral vascular disorders and suppression of stroke recurrence. Previous studies reported that by increasing the activity of NO and PKA, the blood flow of stria vascularis and cochlear hair cells can be improved. These studies implies that cilostazol, which causes inhibition of PDE3 and increase of PKA, can have a potential effect on improvement of tinnitus by increase of blood flow to peripheral cochlear cells. Thus, we hypothesized that cilostazol, which has been widely used for enhancing peripheral blood flow, can bring improvement of tinnitus by causing better peripheral blood flow of cochlea. The aim of the study We planned this study to validate the assumptions of the background. The aim of our study is whether administration of cilostazol can improve tinnitus in terms of subjective degree of symptoms in chronic tinnitus patients.

Detailed Description
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Clinical research methods Determination of eligibility by history taking, physical examination, pure tone audiometry, speech audiometry, and distortion product otoacoustic emission test. Randomization by random sequence generation Administration : cilostazol 100mg Bid 4 weeks for the study group and placebo tablet Bid 4 weeks for the control group. Evaluation battery: questionnaires (tinnitus handicap inventory, visual analogue scale, Quality of life SF-36) Time of evaluation : pre-administration, 2 weeks after administration, 4 week after administration Monitoring of side effects Evaluation of treatment response - Statistical analysis of scores of questionnaires using SPSS K12.0 (paired t-test for changes of each group and Mann-Whitney U test for comparing the mean scores of two groups)

Official Title
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A Randomized, Prospective, Placebo-controlled Double-blind, Pilot Study on the Effect of Cilostazol for 4 Weeks in Patients With Chronic Tinnitus

Conditions
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Tinnitus

Intervention / Treatment
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* Drug: Cilostazol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults of age over 19 Unilateral or bilateral tinnitus Chronic tinnitus lasting more than 3 months Initial visual analogue scale of tinnitus >3 Exclusion Criteria: Conductive hearing loss on pure tone audiometry Associated other inner ear diseases such as Meniere's disease Objective or pulsatile tinnitus Contraindication to anti-platelet drug Any cardiac disease Bleeding tendency and major operation within 3 months Breastfeeding Pregnancy

Ages Eligible for Study
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Minimum Age: 20 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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cilostazol group<br>Administration of Cilostazol 100mg twice a day for 4 weeks | Drug: Cilostazol<br>* Administration of Cilostazol 100mg twice a day for 4 weeks<br>* Other names: Pletaal;|
| Placebo Comparator: Placebo group<br>placebo drug twice a day for 4 weeks. | Drug: Placebo<br>* placebo one tablet matching for cilostazol twice a day for 4 weeks.<br>* Other names: Placebo matching for cilostazol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of the tinnitus handicap inventory (THI) score | A Questionnaire for assessing subjective discomfort from chronic tinnitus | within 2 weeks before administration, 2 weeks after administration, 4 week after administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of Quality of Life (SF-36) score | A questionnaire for assessing subjective discomfort from chronic tinnitus | within 2weeks before administration, 2 weeks after administration, 4 weeks after administration | 
| Change of the visual analogue scale (VAS) score | A Questionnaire for assessing subjective discomfort from chronic tinnitus | within 2 weeks before administration, 2 weeks after administration, 4 week after administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tinnitus, Medication therapy management, Cilostazol, Antiplatelet agents