Gentamicin Treatment Prior to Schwannoma Surgery - Residual Function

Study Overview
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Brief Summary
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The purpose of the study is to determine whether vestibular and postural compensation following schwannoma surgery is improved by ablating remaining vestibular function prior to surgery, through gentamicin injections in the middle ear.

Detailed Description
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The residual function of the vestibular system before surgery differs considerably between patients, due to extent and influence of tumor growth, resulting in varying spectra of post-surgery illness as well as vestibular symptoms. An acute unilateral vestibular deafferentation (uVD) (if significant vestibular function remains prior to surgery) invariably results in severe nausea and vertigo. The nausea/vertigo induced by surgery and sudden uVD both can impede vestibular compensation processes and in extension, also the need for rehabilitation. The vestibular PREHAB protocol was developed in order to address this problem and to ensure an enhanced and sufficient rehabilitation. The protocol encompass treating patients that have measurable vestibular function before surgery with intratympanic gentamicin injections, thus producing gradually a uVD over a period of 3-4 weeks, whilst performing daily vestibular exercises before and after the gentamicin treatment. Through this procedure the sensory trauma is separated from the surgical trauma, making it possible for vestibular compensation to ensue as the vestibular function gradually decline from gentamicin toxicity, unencumbered by any depression of central nervous function that might result from schwannoma surgery or the acute stages of an uVD.

Official Title
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Gentamicin Treatment Prior to Vestibular Schwannoma Surgery in Patients With Definite Remaining Vestibular Function

Conditions
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Vestibular Schwannoma

Intervention / Treatment
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* Drug: Gentamicins


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosed with vestibular schwannoma and surgical treatment is advised remaining vestibular function Exclusion Criteria: impaired decision making no remaining vestibular function signs of central nervous dysfunction neurofibromatosis Patients are advised not to participate in the gentamicin arm but encouraged to participate in the 'non-gentamicin' arm: when hearing is better than 30decibel (dB) i pure tone average (500, 1000, 2000, 3000/4000 Hz) and speech discrimination better than 70% -when the neurosurgeon aim at hearing preservation surgery and do not want to risk gentamicin- associated hearing loss

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gentamicin treated<br>Installation of gentamicin in the middle ear 6 weeks prior to surgery + rehabilitation exercises before and after both treatment and surgery. Rehabilitation exercises are not considered to be an intervention since their benign impact on vestibular/postural compensation is well documented, and exclusion from exercises would not be approved by the ethical board. | Drug: Gentamicins<br>* Intratympanic installation of gentamicin 2-4 times depending on the efficacy of vestibular deafferentation<br>* Other names: Intratympanic installation of gentamicin;|
| No Intervention: Non-gentamicin<br>Rehabilitation exercises before and after surgery. Rehabilitation exercises are not considered to be an intervention since their benign impact on vestibular/postural compensation is well documented, and exclusion from exercises would not be approved by the ethical board. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences and changes of postural control following surgery, compared to before surgery | Postural control assessed with posturography during a sensory conflict | At first vestibular assessment at the time for inclusion and 6 months after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences of duration of hospital stay | Hospital stay required before patients can be discharged | After surgery for the duration of the hospital stay up to two weeks | 
| Differences of subjective well being after surgery | Daily subjective assessment of perceived vertigo/dizziness after surgery and gentamicin treatment | Immediate time after surgery (2 weeks) | 
| Change of subjective well being after gentamicin treatment | Daily subjective assessment of perceived vertigo/dizziness after gentamicin treatment | Immediate time after gentamicin installation (2 weeks) | 
| Change of hearing levels | Measuring hearing levels (pure tone hearing and speech discrimination) before and after gentamicin treatment to determine possible detrimental effect on hearing | At first vestibular assessment and 2 weeks after gentamicin installation | 
| Differences in the level of stress after surgery | Daily Measures of cortisol in the saliva after surgery during the time patients are admitted to the hospital | Daily after surgery for the duration of the hospital stay up to 2 weeks | 
| Differences of perceived dizziness after surgery | Measure of level of impact of dizziness in daily life, measured with Dizziness Handicap Inventory (DHI) | 6 months after surgery | 
| Differences of level of anxiety and depression | Measure of level of anxiety and depression after surgery, enquiry with Hospital Anxiety and Depression Scale (HADS) | 6 months after surgery | 
| Change of level of perceived dizziness after gentamicin | Measure of level of impact of dizziness in daily life, measured with Dizziness Handicap Inventory (DHI) | At first vestibular assessment and 6 weeks after gentamicin installation | 
| Differences of changes in levels of perceived dizziness after surgery as compared to before surgery | Measure of level of impact of dizziness in daily life, measured with Dizziness Handicap Inventory (DHI) | At first vestibular assessment and 6 months after surgery | 
| Occurrence of spontaneous nystagmus after surgery | To measure spontaneous nystagmus after surgery and its direction as a sign of vestibular deafferentation or central nervous damage | Day 1 after surgery and for duration of either spontaneous nystagmus or hospital stay (up to 2 weeks) | 
| Differences in vestibular compensation after surgery | Vestibular function tests, v-HIT, calorics and otolith tests to determine compensation after surgery | 6 months after surgery | 
| Change of vestibular function after gentamicin treatment | Vestibular function tests, v-HIT, calorics and otolith tests to determine compensation and function after gentamicin treatment | 6weeks after gentamicin treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vestibular schwannoma, acoustic neuroma, cerebellopontine angle tumour, gentamicin, rehabilitation, postural balance