Gentamicin Treatment Prior to Schwannoma Surgery - No Residual Function

Gentamicin Treatment Prior to Vestibular Schwannoma Surgery in Patients With no Measurable Remaining Vestibular Function

The purpose of the study is to determine whether vestibular and postural compensation following schwannoma surgery is improved by ablating vestibular function prior to surgery, even if vestibular function is absent according to modern assessment techniques

Study Overview

• Status: Withdrawn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

Detailed Description

Patients subjected to vestibular schwannoma surgery most often suffer from vertigo after surgery, even if no vestibular function can be found in pre-surgical assessment. According to retrospective data about 33% of patients scheduled for surgery do not have any measurable vestibular function. Even the occurrence of spontaneous nystagmus has been recorded in patients with no or very little function prior to surgery (Parietti-Winkler et al. 2008 JNNP). This indicates that despite new methods of measuring vestibular function, remaining vestibular function can be present and patients might benefit from pre-treatment of gentamicin (Tjernström et al. 2009 JNNP)

• 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:

• Vestibular schwannoma advised to surgical treatment
• No measurable remaining vestibular function

Exclusion Criteria:

• impaired decision making
• neurofibromatosis
• signs for central dysfunction
• remaining vestibular function
• Patients are advised not to participate in the gentamicin arm if
• hearing is better than 30 deciBel (dB) in pure tone average (500, 1000, 2000, 3-4000 Hz) and speech discrimination better than 70%
• 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: Gentamicin; Intratympanic installation of gentamicin 2-4 times depending on the efficacy of vestibular deafferentation; Other Names: prehabituation
No Intervention: Non-gentamicin; 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

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
Occurrence of spontaneous nystagmus after surgery	To measure spontaneous nystagmus and its direction after surgery as a sign of vestibular deafferentation or central nervous damage	Day 1 after surgery and for the duration of either spontaneous nystagmus or hospital stay (up to 2 weeks)
Change of hearing levels	Measuring hearing levels (pure tone average and speech discrimination) before and after gentamicin treatment to determine possible detrimental effects on hearing	At first vestibular assessment and 4weeks after gentamicin installation
Differences in the level of stress after surgery	Measuring 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 subjective well being after surgery	Daily subjective assessment of perceived vertigo/dizziness after surgery	Immediate time after surgery (2weeks)
Differences of duration of hospital stay	Length of hospital stay required before patients can be discharged	After surgery for the duration of the hospital stay up to 2 weeks
Differences of subjective well being after gentamicin treatment	Daily subjective assessment of perceived vertigo/dizziness after gentamicin treatment	Immediate time after gentamicin treatment (2weeks)
Differences of perceived dizziness after surgery	Measurement of level of dizziness in daily life, questionnaire Dizziness Handicap Inventory (DHI)	6 months after surgery
Differences of perceived anxiety/depression after surgery	Measurement of level of anxiety/depression in daily life, questionnaire Hospital Anxiety and Depression Scale (HADS)	6 months after surgery
Change of level of perceived dizziness after surgery as compared to before surgery	Measurement of level of dizziness in daily life, questionnaire Dizziness Handicap Inventory (DHI)	At first vestibular assessment (inclusion) and 6 months after surgery
Change of level of perceived anxiety/depression after surgery as compared to before surgery	Measurement of level of anxiety/depression in daily life, questionnaire Hospital Anxiety and Depression Scale (HADS)	At first vestibular assessment (inclusion) and 6 months after surgery
Differences in vestibular compensation after surgery	Vestibular function tests; v-HIT (head impulse test), calorics and otolith tests to determine compensation and function after surgery	6 months after surgery
Change of vestibular function after gentamicin treatment	Vestibular function tests; v-HIT (head impulse test), calorics and otolith tests to determine compensation and function after gentamicin treatment	6 weeks after gentamicin treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences of needed sick-leave from work and leisure activities	Time for return to normal daily activities after surgery, both job-related and leisure.	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.
• Parietti-Winkler C, Gauchard GC, Simon C, Perrin PP. Visual sensorial preference delays balance control compensation after vestibular schwannoma surgery. J Neurol Neurosurg Psychiatry. 2008 Nov;79(11):1287-94. doi: 10.1136/jnnp.2007.135913. Epub 2008 Aug 1.

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Actual): September 1, 2020
• Study Completion (Actual): September 1, 2020

Study Registration Dates

• First Submitted: January 26, 2015
• First Submitted That Met QC Criteria: April 8, 2015
• First Posted (Estimate): April 14, 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; Vestibular schwannoma; postural balance; 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-02