Prevention of Cisplatin-Induced Hearing Loss by Intratympanic Dexamethasone Treatment

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Meir Medical Center
ClinicalTrials.gov Identifier:
NCT01372904
First received: June 13, 2011
Last updated: July 16, 2014
Last verified: July 2014
  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
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Prevention of Cisplatin-Induced Hearing Loss by Intratympanic Dexamethasone Treatment.

Resource links provided by NLM:


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 ] [ Designated as safety issue: No ]
    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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
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: 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

No publications provided

Responsible Party: Meir Medical Center
ClinicalTrials.gov Identifier: NCT01372904     History of Changes
Other Study ID Numbers: CIS 4/2011
Study First Received: June 13, 2011
Last Updated: July 16, 2014
Health Authority: Israel: Clalit Health Services

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
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Protease Inhibitors

ClinicalTrials.gov processed this record on August 26, 2014