Prevention of Cisplatin-Induced Hearing Loss by Intratympanic Dexamethasone Treatment

NCT01372904 | Completed Phase 4

• 1 other identifier: CIS 4/2011
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cisplatin Ototoxicity

Keywords

Cisplatin; Hearing loss; Ototoxicity; Intratympanic injection; Dexamethasone; Steroids; Prevention

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  Two years

Study Arms (1)

Dexamethasone

EXPERIMENTAL

Drug: Dexamethasone Phosphate

Interventions

Dexamethasone Phosphate DRUG

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.

Also known as: Decadron, Dexamethasone Intensol, Dexpak Taperpak, Zema Pak

Dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Meir Medical Center: lead

Study Sites (1)

Clalit Health Services

Haifa, Israel

Location

MeSH Terms

Conditions

Hearing Loss; Ototoxicity

Interventions

dexamethasone 21-phosphate; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pathologic Processes; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Tal M Marshak, MD

  Clalit Health Services

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2011
• First Posted: June 14, 2011
• Study Start: June 1, 2011
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: July 17, 2014

Record last verified: 2014-07

Locations

IL (1)