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Gentamicin Treatment Prior to Schwannoma Surgery - Residual Function

Primary Purpose

Vestibular Schwannoma

Status
Withdrawn
Phase
Phase 4
Locations
Sweden
Study Type
Interventional
Intervention
Gentamicins
Sponsored by
Lund University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Vestibular Schwannoma focused on measuring vestibular schwannoma, acoustic neuroma, cerebellopontine angle tumour, gentamicin, rehabilitation, postural balance

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Gentamicin treated

Non-gentamicin

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Differences and changes of postural control following surgery, compared to before surgery
Postural control assessed with posturography during a sensory conflict

Secondary Outcome Measures

Differences of duration of hospital stay
Hospital stay required before patients can be discharged
Differences of subjective well being after surgery
Daily subjective assessment of perceived vertigo/dizziness after surgery and gentamicin treatment
Change of subjective well being after gentamicin treatment
Daily subjective assessment of perceived vertigo/dizziness after gentamicin treatment
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
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
Differences of perceived dizziness after surgery
Measure of level of impact of dizziness in daily life, measured with Dizziness Handicap Inventory (DHI)
Differences of level of anxiety and depression
Measure of level of anxiety and depression after surgery, enquiry with Hospital Anxiety and Depression Scale (HADS)
Change of level of perceived dizziness after gentamicin
Measure of level of impact of dizziness in daily life, measured with Dizziness Handicap Inventory (DHI)
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)
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
Differences in vestibular compensation after surgery
Vestibular function tests, v-HIT, calorics and otolith tests to determine compensation 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

Full Information

First Posted
January 25, 2015
Last Updated
September 9, 2020
Sponsor
Lund University
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1. Study Identification

Unique Protocol Identification Number
NCT02379754
Brief Title
Gentamicin Treatment Prior to Schwannoma Surgery - Residual Function
Official Title
Gentamicin Treatment Prior to Vestibular Schwannoma Surgery in Patients With Definite Remaining Vestibular Function
Study Type
Interventional

2. Study Status

Record Verification Date
September 2020
Overall Recruitment Status
Withdrawn
Study Start Date
January 2015 (undefined)
Primary Completion Date
June 2019 (Actual)
Study Completion Date
September 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Lund University

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Vestibular Schwannoma
Keywords
vestibular schwannoma, acoustic neuroma, cerebellopontine angle tumour, gentamicin, rehabilitation, postural balance

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Gentamicin treated
Arm Type
Experimental
Arm Description
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.
Arm Title
Non-gentamicin
Arm Type
No Intervention
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Gentamicins
Other Intervention Name(s)
Prehabituation, PREHAB, Intratympanic installation of gentamicin
Intervention Description
Intratympanic installation of gentamicin 2-4 times depending on the efficacy of vestibular deafferentation
Primary Outcome Measure Information:
Title
Differences and changes of postural control following surgery, compared to before surgery
Description
Postural control assessed with posturography during a sensory conflict
Time Frame
At first vestibular assessment at the time for inclusion and 6 months after surgery
Secondary Outcome Measure Information:
Title
Differences of duration of hospital stay
Description
Hospital stay required before patients can be discharged
Time Frame
After surgery for the duration of the hospital stay up to two weeks
Title
Differences of subjective well being after surgery
Description
Daily subjective assessment of perceived vertigo/dizziness after surgery and gentamicin treatment
Time Frame
Immediate time after surgery (2 weeks)
Title
Change of subjective well being after gentamicin treatment
Description
Daily subjective assessment of perceived vertigo/dizziness after gentamicin treatment
Time Frame
Immediate time after gentamicin installation (2 weeks)
Title
Change of hearing levels
Description
Measuring hearing levels (pure tone hearing and speech discrimination) before and after gentamicin treatment to determine possible detrimental effect on hearing
Time Frame
At first vestibular assessment and 2 weeks after gentamicin installation
Title
Differences in the level of stress after surgery
Description
Daily Measures of cortisol in the saliva after surgery during the time patients are admitted to the hospital
Time Frame
Daily after surgery for the duration of the hospital stay up to 2 weeks
Title
Differences of perceived dizziness after surgery
Description
Measure of level of impact of dizziness in daily life, measured with Dizziness Handicap Inventory (DHI)
Time Frame
6 months after surgery
Title
Differences of level of anxiety and depression
Description
Measure of level of anxiety and depression after surgery, enquiry with Hospital Anxiety and Depression Scale (HADS)
Time Frame
6 months after surgery
Title
Change of level of perceived dizziness after gentamicin
Description
Measure of level of impact of dizziness in daily life, measured with Dizziness Handicap Inventory (DHI)
Time Frame
At first vestibular assessment and 6 weeks after gentamicin installation
Title
Differences of changes in levels of perceived dizziness after surgery as compared to before surgery
Description
Measure of level of impact of dizziness in daily life, measured with Dizziness Handicap Inventory (DHI)
Time Frame
At first vestibular assessment and 6 months after surgery
Title
Occurrence of spontaneous nystagmus after surgery
Description
To measure spontaneous nystagmus after surgery and its direction as a sign of vestibular deafferentation or central nervous damage
Time Frame
Day 1 after surgery and for duration of either spontaneous nystagmus or hospital stay (up to 2 weeks)
Title
Differences in vestibular compensation after surgery
Description
Vestibular function tests, v-HIT, calorics and otolith tests to determine compensation after surgery
Time Frame
6 months after surgery
Title
Change of vestibular function after gentamicin treatment
Description
Vestibular function tests, v-HIT, calorics and otolith tests to determine compensation and function after gentamicin treatment
Time Frame
6weeks after gentamicin treatment
Other Pre-specified Outcome Measures:
Title
Differences of needed sick-leave from work and leisure activities
Description
Time to return to normal daily activities after surgery, both job-related and leisure activities
Time Frame
6 months after surgery

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fredrik Tjernström, MD, PhD
Organizational Affiliation
Lund University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dept. OtoRhinoLaryngology Head and Neck Surgery, Skane University Hospital
City
Lund
ZIP/Postal Code
22185
Country
Sweden

12. IPD Sharing Statement

Citations:
PubMed Identifier
1950529
Citation
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.
Results Reference
background
PubMed Identifier
19574236
Citation
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.
Results Reference
result
PubMed Identifier
19645909
Citation
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.
Results Reference
result
PubMed Identifier
22027076
Citation
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.
Results Reference
result
PubMed Identifier
17917842
Citation
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.
Results Reference
result
PubMed Identifier
18607963
Citation
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.
Results Reference
result

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Gentamicin Treatment Prior to Schwannoma Surgery - Residual Function

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