A Study on the Effect of Cilostazol in Patients With Chronic Tinnitus (CITI-ESR)

This study has been completed.
Sponsor:
Collaborator:
Korea Otsuka Pharmaceutical Co.,Ltd.
Information provided by (Responsible Party):
Jong Woo Chung, Asan Medical Center
ClinicalTrials.gov Identifier:
NCT01378650
First received: June 21, 2011
Last updated: May 21, 2014
Last verified: May 2014
  Purpose
  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.

Condition Intervention
Tinnitus
Drug: Cilostazol
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Prospective, Placebo-controlled Double-blind, Pilot Study on the Effect of Cilostazol for 4 Weeks in Patients With Chronic Tinnitus

Resource links provided by NLM:


Further study details as provided by Asan Medical Center:

Primary Outcome Measures:
  • Change of the tinnitus handicap inventory (THI) score [ Time Frame: within 2 weeks before administration, 2 weeks after administration, 4 week after administration ] [ Designated as safety issue: No ]
    A Questionnaire for assessing subjective discomfort from chronic tinnitus


Secondary Outcome Measures:
  • Changes of Quality of Life (SF-36) score [ Time Frame: within 2weeks before administration, 2 weeks after administration, 4 weeks after administration ] [ Designated as safety issue: No ]
    A questionnaire for assessing subjective discomfort from chronic tinnitus

  • Change of the visual analogue scale (VAS) score [ Time Frame: within 2 weeks before administration, 2 weeks after administration, 4 week after administration ] [ Designated as safety issue: No ]
    A Questionnaire for assessing subjective discomfort from chronic tinnitus


Enrollment: 50
Study Start Date: July 2011
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cilostazol group
Administration of Cilostazol 100mg twice a day for 4 weeks
Drug: Cilostazol
Administration of Cilostazol 100mg twice a day for 4 weeks
Other Name: Pletaal
Placebo Comparator: Placebo group
placebo drug twice a day for 4 weeks.
Drug: Placebo
placebo one tablet matching for cilostazol twice a day for 4 weeks.
Other Name: Placebo matching for cilostazol

Detailed 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)
  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01378650

Locations
Korea, Republic of
Asan Medical Center
Seoul, Korea, Republic of, 138-736
Sponsors and Collaborators
Jong Woo Chung
Korea Otsuka Pharmaceutical Co.,Ltd.
Investigators
Principal Investigator: Jong Woo Chung, M.D. Asan Medical Center
  More Information

Additional Information:
Publications:
Responsible Party: Jong Woo Chung, MD, Asan Medical Center
ClinicalTrials.gov Identifier: NCT01378650     History of Changes
Other Study ID Numbers: AMC-2010-0800, KCT0000128
Study First Received: June 21, 2011
Last Updated: May 21, 2014
Health Authority: South Korea: Korea Food and Drug Administration (KFDA)

Keywords provided by Asan Medical Center:
Tinnitus
Medication therapy management
Cilostazol
Antiplatelet agents

Additional relevant MeSH terms:
Tinnitus
Hearing Disorders
Ear Diseases
Otorhinolaryngologic Diseases
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Cilostazol
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Vasodilator Agents
Neuroprotective Agents
Protective Agents
Central Nervous System Agents
Phosphodiesterase 3 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 26, 2014