Prevention of Cisplatin-Induced Hearing Loss by Intratympanic Dexamethasone Treatment

This study has been completed.

Sponsor:

ClinicalTrials.gov Identifier:

NCT01372904

First Posted: June 14, 2011

Last Update Posted: July 17, 2014

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Information provided by (Responsible Party):

Meir Medical Center

Purpose

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.

Condition	Intervention	Phase
Cisplatin Ototoxicity	Drug: Dexamethasone Phosphate	Phase 4


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Prevention
Official Title:	Prevention of Cisplatin-Induced Hearing Loss by Intratympanic Dexamethasone Treatment.

Resource links provided by NLM:

Genetics Home Reference related topics: nonsyndromic hearing loss

MedlinePlus related topics: Hearing Disorders and Deafness

Drug Information available for: Dexamethasone Dexamethasone phosphate Dexamethasone sodium phosphate Cisplatin Dexamethasone acetate

U.S. FDA Resources

Further study details as provided by Meir Medical Center:

Primary Outcome Measures:

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. [ Time Frame: 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.


Enrollment:	30
Study Start Date:	June 2011
Study Completion Date:	June 2013
Primary Completion Date:	June 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Dexamethasone	Drug: Dexamethasone Phosphate 0.7ml of Dexamethasone Phosphate 10mg/ml would be injected unilaterally to the middle ear using 25 gauge spinal needle. The trans-tympanic membrane injection would take place at the posterior inferior quadrant of the ear drum facing the round window niche. The patient would be instructed to lie down for 20 minutes after the injection with the treated side up and to avoid swallowing or coughing. Intratympanic Dexamethasone would be delivered immediately prior to each cisplatin treatment as maximal level. Other Name: Decadron, Dexamethasone Intensol, Dexpak Taperpak, Zema Pak

Arms

Assigned Interventions

Experimental: Dexamethasone

Drug: Dexamethasone Phosphate

0.7ml of Dexamethasone Phosphate 10mg/ml would be injected unilaterally to the middle ear using 25 gauge spinal needle.

The trans-tympanic membrane injection would take place at the posterior inferior quadrant of the ear drum facing the round window niche. The patient would be instructed to lie down for 20 minutes after the injection with the treated side up and to avoid swallowing or coughing. Intratympanic Dexamethasone would be delivered immediately prior to each cisplatin treatment as maximal level.

Other Name: Decadron, Dexamethasone Intensol, Dexpak Taperpak, Zema Pak

Show Detailed Description

Eligibility

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01372904

Locations


Israel
Clalit Health Services
Haifa, Israel

Sponsors and Collaborators

Meir Medical Center

Investigators


Principal Investigator:	Tal M Marshak, MD	Clalit Health Services

More Information


Responsible Party:	Meir Medical Center
ClinicalTrials.gov Identifier:	NCT01372904 History of Changes
Other Study ID Numbers:	CIS 4/2011
First Submitted:	June 13, 2011
First Posted:	June 14, 2011
Last Update Posted:	July 17, 2014
Last Verified:	July 2014

Keywords provided by Meir Medical Center:


Cisplatin Hearing loss Ototoxicity Intratympanic injection	Dexamethasone Steroids Prevention

Additional relevant MeSH terms:


Hearing Loss Deafness Hearing Disorders Ear Diseases Otorhinolaryngologic Diseases Sensation Disorders Neurologic Manifestations Nervous System Diseases Signs and Symptoms Cisplatin Dexamethasone Dexamethasone acetate Dexamethasone 21-phosphate BB 1101	Antineoplastic Agents Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action

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