Gentamicin Treatment Prior to Schwannoma Surgery - Residual Function

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Vestibular Schwannoma
• Intervention / Treatment: Drug: Gentamicins

Detailed Description

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.

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• Sweden
  • Lund, Sweden, 22185
    • Dept. OtoRhinoLaryngology Head and Neck Surgery, Skane University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gentamicin treated; 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; Intratympanic installation of gentamicin 2-4 times depending on the efficacy of vestibular deafferentation; Other Names: Prehabituation, PREHAB; Intratympanic installation of gentamicin
No Intervention: Non-gentamicin; 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?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences of needed sick-leave from work and leisure activities	Time to return to normal daily activities after surgery, both job-related and leisure activities	6 months after surgery

Collaborators and Investigators

• Sponsor: Lund University
• Investigators: Principal Investigator: Fredrik Tjernström, MD, PhD, Lund University

Publications and helpful links

General Publications

• Magnusson M, Padoan S. Delayed onset of ototoxic effects of gentamicin in treatment of Meniere's disease. Rationale for extremely low dose therapy. Acta Otolaryngol. 1991;111(4):671-6. doi: 10.3109/00016489109138398.
• Tjernstrom F, Fransson PA, Kahlon B, Karlberg M, Lindberg S, Siesjo P, Magnusson M. Vestibular PREHAB and gentamicin before schwannoma surgery may improve long-term postural function. J Neurol Neurosurg Psychiatry. 2009 Nov;80(11):1254-60. doi: 10.1136/jnnp.2008.170878. Epub 2009 Jul 1.
• Magnusson M, Kahlon B, Karlberg M, Lindberg S, Siesjo P, Tjernstrom F. Vestibular "PREHAB". Ann N Y Acad Sci. 2009 May;1164:257-62. doi: 10.1111/j.1749-6632.2009.03778.x.
• Magnusson M, Karlberg M, Tjernstrom F. 'PREHAB': Vestibular prehabilitation to ameliorate the effect of a sudden vestibular loss. NeuroRehabilitation. 2011;29(2):153-6. doi: 10.3233/NRE-2011-0689.
• Magnusson M, Kahlon B, Karlberg M, Lindberg S, Siesjo P. Preoperative vestibular ablation with gentamicin and vestibular 'prehab' enhance postoperative recovery after surgery for pontine angle tumours--first report. Acta Otolaryngol. 2007 Dec;127(12):1236-40. doi: 10.1080/00016480701663433.
• Postema RJ, Kingma CM, Wit HP, Albers FW, Van Der Laan BF. Intratympanic gentamicin therapy for control of vertigo in unilateral Menire's disease: a prospective, double-blind, randomized, placebo-controlled trial. Acta Otolaryngol. 2008 Aug;128(8):876-80. doi: 10.1080/00016480701762458.

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): June 1, 2019
• Study Completion (Actual): September 1, 2020

Study Registration Dates

• First Submitted: January 25, 2015
• First Submitted That Met QC Criteria: March 1, 2015
• First Posted (Estimate): March 5, 2015

Study Record Updates

• Last Update Posted (Actual): September 11, 2020
• Last Update Submitted That Met QC Criteria: September 9, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: rehabilitation; gentamicin; postural balance; vestibular schwannoma; acoustic neuroma; cerebellopontine angle tumour
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Otorhinolaryngologic Neoplasms; Otorhinolaryngologic Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Ear Diseases; Nervous System Neoplasms; Cranial Nerve Diseases; Neuroendocrine Tumors; Nerve Sheath Neoplasms; Peripheral Nervous System Neoplasms; Cranial Nerve Neoplasms; Neuroma; Vestibulocochlear Nerve Diseases; Retrocochlear Diseases; Neurilemmoma; Neuroma, Acoustic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Gentamicins
• Other Study ID Numbers: VS-FT-01