Prevention of Cisplatin-Induced Hearing Loss by Intratympanic Dexamethasone Treatment.
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Examine possible protective effect of IT dexamethasone on cisplatin-induced hearing loss. Hearing assessment would include:pure tone, speech and impedance audiometry, and Distortion Product Otoacoustic Emissions (DPOAEs) testing.
研究概览
简要总结
Cisplatin is a widely used chemotherapeutic agent for the treatment of various malignant neoplasms, including testicular, ovarian, bladder, cervix uteri, head and neck and lung cancers.
One of the common side-effects of this drug is bilateral, symmetric, progressive and usually irreversible sensorineural hearing loss.
Cisplatin induces cochlear toxicity by the production of reactive oxygen species (ROS).
Dexamethasone treatment is currently practiced for various pathologies afflicting the inner ear. The positive effect of Dexamethasone is attributed to it's anti ROS activity and it's capability to up-regulate cochlear anti ROS enzymes.
In order to reach higher inner ear concentration of the drug while avoiding it's undesirable systemic side-effects, Intratympanic (IT) delivery of Dexamethasone became vastly used in the last decades for the treatment of sudden sensorineural hearing loss and Meniere's disease.
Dexamethasone inserted IT, diffuse across the round window into the inner ear perilymph where it exerts its therapeutic effects.
The investigators review of the literature yielded three animal studies which examined the protective effect of IT dexamethasone in the prevention of cisplatin-induced hearing loss. These studies demonstrated promising results pointing to the potential for IT dexamethasone in the prevention of cisplatin ototoxicity in humans.
The purpose of this study is to examine possible protective effect of IT dexamethasone on cisplatin-induced hearing loss, in humans.
The study hypothesis is that IT dexamethasone treatment would prevent cisplatin-induced hearing loss.
详细描述
Prevention of Cisplatin-Induced Hearing Loss by Intratympanic Dexamethasone Treatment.
Introduction:
Cisplatin is a widely used chemotherapeutic agent for the treatment of various malignant neoplasms, including testicular, ovarian, bladder, cervix uteri, head and neck and lung cancers 1-4.
Dose limiting side effects of Cisplatin include nephrotoxicity, neurotoxicity and ototoxicity. While nephrotoxicity can be diminished or controlled with hydration therapy there are no known cure or preventive treatments available for neurotoxicity and ototoxicity 2,4.
Cisplatin-associated ototoxicity is characterized by bilateral, symmetric progressive and usually irreversible sensorineural hearing loss. The hearing impairment is dose related, cumulative and takes place within hours to days from the administration of cisplatin 1-4. The reported incidence of cisplatin-induced hearing loss is variable. Schweitzer calculated from a large number of studies an average incidence of 62% with a range from 11 to 97% 5-6. Damage from cisplatin initially affects the outermost row of outer hair cells located at the cochlear basal turn, which codes hearing at the high frequency range. Further insult affects the remaining rows of outer hair cells, inner hair cells, and supporting cells. The pattern of destruction proceeds from the basal turn towards the more apical regions of the cochlea, with increasing impact on hearing acuity in lower frequencies 7.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients suffering from a neoplastic disease for which the treatment protocol includes cisplatinum not previously delivered to them.
- •The cumulative cisplatin dose would be at least 300mg.
排除标准
- •Age < 18 years.
- •Existing or previous pathology of the external or middle ear avoiding IT drug delivery or the performance of DPOAEs testing.
- •Retrocochlear hearing loss.
- •Meniere's disease.
- •Autoimmune Inner Ear Disease.
- •fluctuating hearing loss.
- •History of sudden sensory neural hearing loss.
- •Previous radiation therapy to the head and neck region.
- •Baseline average pure tone audiometry thresholds for 500-3000 Hz and 4000-8000 Hz greater than 40 dB.
- •Average SNR below 6 dB for DPOAEs f2 frequencies 500-3000 Hz and 4000-8000 Hz.
研究组 & 干预措施
Dexamethasone
干预措施: Dexamethasone Phosphate (Drug)
结局指标
主要结局
Examine possible protective effect of IT dexamethasone on cisplatin-induced hearing loss. Hearing assessment would include:pure tone, speech and impedance audiometry, and Distortion Product Otoacoustic Emissions (DPOAEs) testing.
时间窗: Two years
Distortion Product Otoacoustic Emissions (DPOAEs) testing is a test that specifically evaluates the functioning of the cochlear outer hair cells which are the primary target organ for cisplatin ototoxicity.
次要结局
未报告次要终点