Transtympanic Gentamicin vs. Steroids in Refractory Meniere's Disease

Study Overview
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Brief Summary
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This trial aims to compare transtympanic steroids against the standard treatment (transtympanic gentamicin) in refractory unilateral Meniere's disease.

Detailed Description
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Meniere's disease is characterised by episodic spontaneous vertigo attacks with hearing loss, ringing sounds and fullness in the ear. In one out of five patients, standard first line medical treatment is not effective in controlling vertigo attacks. For these incapacitated patients, gentamicin injections through the ear drum is a well established minimally invasive treatment. Major surgery of the balance organs or nerve, risking complete hearing loss, CSF leak, meningeal infections, are rarely performed nowadays. Gentamicn is very effective in controlling vertigo and acts by chemical ablation of end organs. As hearing and balance organs are entwined around each other, gentamicin treatment does not come without the risk of hearing loss. In fact, meta-analysis shows hearing deterioration in 13% to 35% percent of gentamicin treated patients. On the other hand, steroids are drug of choice for autoimmune inner ear disease and commonly used for sudden hearing loss. They are non toxic drugs without any known side effects during local treatment in ear. We will compare the two in this randomised, double blind trial.

Official Title
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Effectiveness of Transtympanic Steroids in Unilateral Ménière's Disease: a Randomised Controlled Double-Blind Trial

Conditions
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Meniere's Disease

Intervention / Treatment
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* Drug: Methylprednisolone
* Drug: Gentamicin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with unilateral Ménière's disease (definite or probable, according to Committee on Hearing and Equilibrium guidelines, 1995) with hearing loss and presenting with recurrent vertigo, not responding to medical treatment for at least 6 months will be included. There should be normal, age appropriate hearing in the contralateral ear. Exclusion Criteria: Patients with Ménière's disease in later stages (not having vertigo attacks). Age: patients older than 70 years at the start of the trial. Severe disability (e.g. neurological, orthopaedic, cardiovascular) or serious concurrent illness that might interfere with treatment or follow up. Active additional neuro-otological disorders that may mimic Ménière's disease (e.g. vestibular migraine, vertebro-basilar TIAs, acoustic neuroma) and thus will make the objective follow up difficult. Concurrent ear pathology that may interfere with transtympanic treatment (e.g. active middle ear disease). Family history of unexplained deafness (possibility of genetic susceptibility to gentamicin toxicity). History of known adverse/allergic reaction to steroids or gentamicin.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Steroid (Methylprednisolone)<br>Steroid (Methylprednisolone) | Drug: Methylprednisolone<br>* 2 transtympanic injections at interval of two weeks.<br>|
| Active Comparator: Gentamicin<br>Gentamicin | Drug: Gentamicin<br>* 2 transtympanic injections at an interval of two weeks. If there is significant hearing loss before second injection, it will be replaced by normal saline in double blinded fashion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vertigo Attacks | The number of vertigo attacks between 18-24months follow-up were taken retrospectively during a face-to-face appointment at 24 months follow-up and compared to 6 month pre-enrollment baseline (as per Committee on Hearing and Equilibrium guidelines). | 6month pre-enrollment baseline, 18-24 months after initial treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hearing | Hearing was measured as ipsilesional pure-tone threshold at Baseline, 1month, 2months, 6months, 12month, 18months and 24 months follow-up. Hearing level was taken as the average threshold across 0.5, 1, 2 and 3KHz. | Baseline, 1,2,6,12,18 and 24months after initial treatment | 
| Change in Speech Discrimination | Speech discrimination was measured at Baseline, 1month, 2months, 6months, 12month and 24 months follow-up. Speech discrimination was assessed by means of ipsilesional suprathreshold word recognition (%). Arthur Boothroyd's isophonemic word lists (AB wordlists, Guymark, Southampton) comprising sets of 10 words were played to the ipsilesional ear at the low-frequency pure-tone threshold of 0·5, 1 and 2 kHz +30dB with masking sound in the contralesional ear if necessary. The formula for masking level was: low-frequency pure-tone threshold in ipsilesional ear - bone conduction mean threshold (0·5, 1 and 2KHz) in contralesional ear - 40dB. Speech loudness and masking were rounded to the nearest 5dB. Step increments and decrements of 10dB for speech loudness and masking were used to attain the maximum speech discrimination score. | Baseline, 1,2,6,12 and 24months after initial treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Meniere's disease, transtympanic steroids, Randomised controlled trial