Deep Brain Stimulation for Tinnitus

Study Overview
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Brief Summary
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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 ís 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, it is known 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. The investigators found in animal studies that DBS in the central auditory pathway can indeed significantly decrease tinnitus-like behavior. In a questionnaire study the investigators 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, the investigators 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), the investigators selected the medial geniculate body of the thalamus (MGB) as the most potential target to treat tinnitus with DBS.

Official Title
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Deep Brain Stimulation for Refractory Tinnitus

Conditions
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Tinnitus

Intervention / Treatment
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* Device: Deep Brain Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Medically refractory tinnitus. Patient does not respond to available tinnitus treatments (hearing aids, cognitive treatments) and is thoroughly evaluated by the multidisciplinary tinnitus team in MUMC. Thus patients do not respond to both of the following treatments (i.e. TQ is still ≥ 47): Hearing aids (except if hearing is normal) 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: Not pulsatile Unilateral or bilateral Severe tinnitus (based on the TQ score ≥ 47) 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. A psychiatrist will screen the patients for this matter. Depression or anxiety disorder which was already present before tinnitus. A psychiatrist will screen the patients for this matter. 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 implantable electronic devices that potentially could interfere with DBS, e.g. cochlear implants, auditory brainstem implants or cortical implants

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 69 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Clinical intervention study (double blind, randomized cross-over design). Two different stimulation paradigms will be investigated: ON and OFF stimulation.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ON-OFF<br>Patients receive the same baseline, a 6 week period of stimulation ON (masked for both patient and investigator), one week of washout, a 6 week period of stimulation OFF (masked for both patient and investigator), one week of washout, a 6 month follow-up period of open-label stimulation ON. | Device: Deep Brain Stimulation<br>* High frequency deep brain stimulation in the medial geniculate body of the thalamus.<br>|
| Experimental: OFF-ON<br>Patients receive the same baseline, a 6 week period of stimulation OFF (masked for both patient and investigator), one week of washout, a 6 week period of stimulation ON (masked for both patient and investigator), one week of washout, a 6 month follow-up period of open-label stimulation ON. | Device: Deep Brain Stimulation<br>* High frequency deep brain stimulation in the medial geniculate body of the thalamus.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change over time of the score on the Tinnitus Functional Index | A validated questionnaire which assesses the impact of tinnitus on a patient measured on multiple time points to measure a change over time. The TFI score can range from 0-100, higher values indicate more tinnitus burden. When a patient scores 54 or higher the tinnitus is considered to be a major problem. | Week 1, week 20, week 26, week 33, week 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| VAS Loudness | on a scale from 0 (no tinnitus) to 10 (most severe tinnitus imaginable), subjects rate their tinnitus perception on loudness. | Week 1, week 12, week 20, week 26, week 33, week 60 | 
| VAS Burden | on a scale from 0 (no tinnitus) to 10 (most severe tinnitus imaginable), subjects rate their tinnitus perception amount of discomfort. | Week 1, week 12, week 20, week 26, week 33, week 60 | 
| 15 word memory test | Participants are given a list of 15 unrelated words repeated over five different trials and are asked to repeat. Another list of 15 unrelated words are given and the client must again repeat the original list of 15 words and then again after 30 minutes. | Week 1, week 27, week 34, week 60 | 
| Boston naming test | The neurpsychologist shows the person each of the pictures, one at a time in the given order. The person is given 20 seconds to say what the drawing depicts. | Week 1, week 27, week 34, week 60 | 
| Stroop Color and Word Test | This is a neuropsychological test used to assess the ability to inhibit cognitive interference that occurs when the processing of a specific stimulus feature impedes the simultaneous processing of a second stimulus attribute, well-known as the Stroop Effect. | Week 1, week 27, week 34, week 60 | 
| Trail Making Test | This is a neuropsychological test of visual attention and task switching. It consists of two parts in which the subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy. | Week 1, week 27, week 34, week 60 | 
| Semantic Verbal Fluency Test (Animals) | This is a test in which participants have to produce as many words as possible from a category, here animals. | Week 1, week 27, week 34, week 60 | 
| Semantic Verbal Fluency Test (Jobs) | This is a test in which participants have to produce as many words as possible from a category, here jobs. | Week 1, week 27, week 34, week 60 | 
| Phonemic Verbal Fluency Test (D) | This is a test in which participants have to produce as many words as possible from a category, here words starting with the letter D. | Week 1, week 27, week 34, week 60 | 
| Phonemic Verbal Fluency Test (A) | This is a test in which participants have to produce as many words as possible from a category, here words starting with the letter A. | Week 1, week 27, week 34, week 60 | 
| Phonemic Verbal Fluency Test (T) | This is a test in which participants have to produce as many words as possible from a category, here words starting with the letter T. | Week 1, week 27, week 34, week 60 | 
| Quality of life Questionnaire | The Short Form (36) Health Survey (standard validated questionnaire) | Week 1, week 27, week 34, week 60 | 
| Beck Depression Inventory II (BDI-II) | Validated questionnaire for depression. | Week 1, week 60 | 
| Beck Anxiety Inventory (BAI) | Validated questionnaire for anxiety. | Week 1, week 60 | 
| Hospital Anxiety and Depression Scale (HADS) | Validated questionnaire for anxiety and depression. | Week 1, week 60 | 
| Audiometry | pure-tone and speech audiometry. These are the clinical standard audiometric tests. | Week 1, week 14, week 27, week 34, week 60 | 
| Auditory Brainstem Response | Neurophysiological measure following standard protocols. | Week 1, week 14, week 27, week 34, week 60 | 
| Electroencephalography (EEG) | Neurophysiological measure following standard protocols. | Week 1, week 14, week 27, week 34, week 60 | 
| Local Field Potentials (LFP) | Neurophysiological measure following standard protocols. | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tinnitus, Deep Brain Stimulation