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

Tinnitus Clinical Trial

— CITI-ESR  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01378650
• Other study ID #: AMC-2010-0800
• Secondary ID: KCT0000128
• Status: Completed
• Phase: N/A
• First received: June 21, 2011
• Last updated: May 21, 2014
• Start date: July 2011
• Est. completion date: June 2013

Study information

• Verified date: May 2014
• Source: Asan Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Korea: Korea Food and Drug Administration (KFDA)
• Study type: Interventional

Clinical Trial Summary

1. 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.

2. 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.

3. 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.

Description:

1. 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

2. 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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Tinnitus

Intervention

Drug:
• Cilostazol
Administration of Cilostazol 100mg twice a day for 4 weeks
• Placebo
placebo one tablet matching for cilostazol twice a day for 4 weeks.

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
Jong Woo Chung	Korea Otsuka Pharmaceutical Co.,Ltd.

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (2)

Mazurek B, Haupt H, Szczepek AJ, Sandmann J, Gross J, Klapp BF, Kiesewetter H, Kalus U, Stöver T, Caffier PP. Evaluation of vardenafil for the treatment of subjective tinnitus: a controlled pilot study. J Negat Results Biomed. 2009 Feb 17;8:3. doi: 10.1186/1477-5751-8-3. — View Citation

Ye YL, Shi WZ, Zhang WP, Wang ML, Zhou Y, Fang SH, Liu LY, Zhang Q, Yu YP, Wei EQ. Cilostazol, a phosphodiesterase 3 inhibitor, protects mice against acute and late ischemic brain injuries. Eur J Pharmacol. 2007 Feb 14;557(1):23-31. Epub 2006 Nov 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No

External Links

•   Clinical Research Information Service (CRIS)
•   Institutional Review Board of Asan Medical Center