The goal is to assess the effect of MGB-DBS on tinnitus severity. Secondary objectives are:- To assess side effects of MGB-DBS on hearing and neuropsychological functioning.- To explore neurophysiological hallmarks.
ID
Source
Brief title
Condition
- Aural disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main endpoint is tinnitus severity, identified by means of a questionnaire,
the Tinnitus Function Index (TFI), which is validated in Dutch. The TFI will be
measured on a regular basis depending on the stage the study is in.
Secondary outcome
Secondary endpoints:
- Tinnitus loudness and burden, both identified by means of Visual Analogue
Scales (VAS). The VAS will be measured regularly.
- Neuropsychological outcome: cognitive functioning (test battery), quality of
life (36-Item Short Form Health Survey; SF-36), depression and anxiety (Beck
Depression Inventory II; BDI-II, Beck Anxiety Inventory; BAI)
- Audiological evaluation: pure-tone and speech audiometry, auditory brainstem
responses (ABR).
- Electrophysiological measurements: EEG, local field potentials.
Background summary
Tinnitus is the perception of a sound in the absence of an audible source.
Currently up to 15% of the general population suffers chronically from
tinnitus. The most severe degree of tinnitus is experienced by 2.4% of the
population and is associated with insomnia, depression, anxiety and even
suicide. Up to date there is no effective standard therapy. Current therapies
mostly focus on treating the distress caused by tinnitus instead of reducing
the actual phantom sound. Nevertheless, many patients do not benefit from the
current approaches and become severe and chronic tinnitus sufferers. In these
patients neuromodulation-based treatments can be a promising option.
Tinnitus perception is associated with many complex changes in several
different brain structures. The general accepted hypothesis is that neuronal
changes occur in both auditory and non-auditory brain structures, most often as
a compensating mechanism on reduced input from the auditory nerve caused by
cochlear hair cell damage. These central neuronal changes include an increase
in spontaneous firing rate, synchronized activity, bursting activity and
tonotopic reorganization.
In high-frequency deep brain stimulation (DBS) a reversible lesion-like effect
is mimicked. From findings in Parkinson*s disease patients who also had
tinnitus and were treated with DBS, we know that stimulation can alter or even
completely diminish perception of tinnitus. It can be expected that modulation
of specific structures within the complex tinnitus pathways can disrupt
pathological neuronal activity and thereby alter tinnitus perception or
distress caused by this phantom sensation. We found in animal studies that DBS
in the central auditory pathway can indeed significantly decrease tinnitus-like
behavior. In a questionnaire study we found that around one-fifth of the
patients would be reasonably willing to accept invasive treatments and
one-fifth would be fully willing to undergo invasive treatment like DBS.
Based on preclinical studies and human case studies, we expect that DBS of the
central auditory pathway will inhibit tinnitus perception and distress caused
by this phantom sensation. Based on studies performed within Maastricht
University Medical Center (MUMC), we selected the medial geniculate body of the
thalamus (MGB) as the most potential target to treat tinnitus with DBS.
Study objective
The goal is to assess the effect of MGB-DBS on tinnitus severity.
Secondary objectives are:
- To assess side effects of MGB-DBS on hearing and neuropsychological
functioning.
- To explore neurophysiological hallmarks.
Study design
Clinical intervention study (double blind, randomized cross-over design). Two
different stimulation paradigms will be investigated: ON and OFF stimulation.
Intervention
Subjects will receive bilateral DBS electrodes, radiologically and
electrophysiologically guided in the MGB of the thalamus, following a standard
surgical procedure.
Study burden and risks
Implantation of DBS electrodes is a routine surgical procedure at Maastricht
University Medical Center (MUMC). Complications can be defined as follows:
1. The complications that can arise from the operation include small bleeding
in the brain that does not cause any symptoms (chance between 1-5%), brain
haemorrhages or cerebral infarctions, which may cause unilateral paralysis
(chance less than 1%) or death (less chance than 0.4%) temporary headache after
the operation, and seizures in 0-5% (which have no lasting consequences). As
with any operation, (wound) infections can occur. Very often (approximately in
1%) the electrodes have to be removed. Also, defects can occur on the device
(in 10-75%) such as a battery that has run out or a cable that is broken. This
can usually be solved easily, but in a number of cases a reoperation is
required to replace the defective part.
2. Side effects caused by deep brain stimulation: when electrical stimulation
is given this has an effect on the brain structure in which the electrode lies,
and to a lesser extent on structures surrounding it. The risks of the
electrical stimulation of the MGB are expected to be small, but could mean
auditory deprivation or auditory sensation. These side effects are expected to
be reversible by switching off the stimulation. The stimulation parameters will
be optimized during the first 6 weeks after surgery during the weekly visits.
Stimulation can be turned off. In the worst case, the entire electrode can be
removed without any residual damage.
3. The risk is that treatment (DBS) has little or no effect on the condition
(tinnitus)
The benefit of this treatment can be a reduction in the loudness of the
tinnitus sound and tinnitus with an improvement in quality of life as a result.
P. Debyelaan 25
Maastricht 6229 HX
NL
P. Debyelaan 25
Maastricht 6229 HX
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all
of the following criteria, all by consideration of the multidisciplinary expert
group:, • Medically refractory tinnitus. Patient does not respond to available
tinnitus treatment and is thoroughly evaluated by the multidisciplinary
tinnitus team in MUMC. Available tinnitus treatments are hearing aids (except
if hearing is normal) and evidence-based cognitive treatment in Hoensbroek
(Cima et al., 2012) or a similar version of this treatment in the MUMC
• Minimum age 18 years, maximum age 69 years.
• Experiencing tinnitus which is:
o Not pulsatile
oUnilateral or bilateral
o Severe tinnitus (based on the TQ score >= 47)
o Chronic and stable (present > 2 years and stable > 1 year).
• Bilateral hearing of high tone Fletcher Index < 60 dB
• Willingness to participate in this study (informed consent)
Exclusion criteria
• Anatomic cause of tinnitus (e.g. vestibular schwannoma, tumour, middle-ear
pathology)
• DSM-V psychiatric disorders, other than depression or anxiety disorder (such
as bipolar disorder, dementia, addiction, personality disorders); diagnosed by
a psychiatrist
• Depression or anxiety disorder which was already present before tinnitus
• Cognitive impairment (assessed with standard *cognitive functioning battery
test* questionnaires) or coping problems (CISS-21)
• Active ear diseases that needs further attention according to research team
• Pregnancy or breast-feeding
• Active suicide thoughts or attempts
• Underlying malignancies, whenever life expectancy is lower than 2 years
• Other exclusion criteria are the same as for the standard DBS operation in
clinical care: significant cerebral atrophy, multiple white matter lesions or
focal brain anomalies.
• Contra-indication for Magnetic Resonance Imaging (claustrophobia or implanted
metal objects such as cardiac pacemakers, intracardiac lines, implanted
medication pumps, implanted electrodes in the brain, other intracranial metal
objects with the exception of dental fillings).
• Also general contra-indications for surgery are considered as exclusion
criteria, e.g. coagulopathies, The specialist team can decide on clinical
grounds that a patient does or does not qualify for MGB-DBS treatment.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| CCMO | NL67027.068.18 |