Clinical trial NCT03976908: Deep Brain Stimulation for Tinnitus
Official title: Deep Brain Stimulation for Refractory Tinnitus
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Tinnitus
Keywords: Tinnitus
Deep Brain Stimulation
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
First posted: 2019-06-06
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Clinical intervention study (double blind, randomized cross-over design). Two different stimulation paradigms will be investigated: ON and OFF stimulation.
Primary purpose: TREATMENT

Brief 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 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change over time of the score on the Tinnitus Functional Index
timeFrame: Week 1, week 20, week 26, week 33, week 60
Secondary outcomes:
measure: VAS Loudness
timeFrame: Week 1, week 12, week 20, week 26, week 33, week 60
measure: VAS Burden
timeFrame: Week 1, week 12, week 20, week 26, week 33, week 60
measure: 15 word memory test
timeFrame: Week 1, week 27, week 34, week 60
measure: Boston naming test
timeFrame: Week 1, week 27, week 34, week 60
measure: Stroop Color and Word Test
timeFrame: Week 1, week 27, week 34, week 60
measure: Trail Making Test
timeFrame: Week 1, week 27, week 34, week 60
measure: Semantic Verbal Fluency Test (Animals)
timeFrame: Week 1, week 27, week 34, week 60
measure: Semantic Verbal Fluency Test (Jobs)
timeFrame: Week 1, week 27, week 34, week 60
measure: Phonemic Verbal Fluency Test (D)
timeFrame: Week 1, week 27, week 34, week 60
measure: Phonemic Verbal Fluency Test (A)
timeFrame: Week 1, week 27, week 34, week 60
measure: Phonemic Verbal Fluency Test (T)
timeFrame: Week 1, week 27, week 34, week 60
measure: Quality of life Questionnaire
timeFrame: Week 1, week 27, week 34, week 60
measure: Beck Depression Inventory II (BDI-II)
timeFrame: Week 1, week 60
measure: Beck Anxiety Inventory (BAI)
timeFrame: Week 1, week 60
measure: Hospital Anxiety and Depression Scale (HADS)
timeFrame: Week 1, week 60
measure: Audiometry
timeFrame: Week 1, week 14, week 27, week 34, week 60
measure: Auditory Brainstem Response
timeFrame: Week 1, week 14, week 27, week 34, week 60
measure: Electroencephalography (EEG)
timeFrame: Week 1, week 14, week 27, week 34, week 60
measure: Local Field Potentials (LFP)
timeFrame: Week 12
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: MUMC+
Study officials:
affiliation: Maastricht University Medical Center
name: Mark Janssen, Dr.
role: PRINCIPAL_INVESTIGATOR
References: