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Deep Brain Stimulation for Tinnitus

Primary Purpose

Tinnitus

Status
Recruiting
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
Deep Brain Stimulation
Sponsored by
Maastricht University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Tinnitus focused on measuring Tinnitus, Deep Brain Stimulation

Eligibility Criteria

18 Years - 69 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • MUMC+Recruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

ON-OFF

OFF-ON

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

VAS Loudness
on a scale from 0 (no tinnitus) to 10 (most severe tinnitus imaginable), subjects rate their tinnitus perception on loudness.
VAS Burden
on a scale from 0 (no tinnitus) to 10 (most severe tinnitus imaginable), subjects rate their tinnitus perception amount of discomfort.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Quality of life Questionnaire
The Short Form (36) Health Survey (standard validated questionnaire)
Beck Depression Inventory II (BDI-II)
Validated questionnaire for depression.
Beck Anxiety Inventory (BAI)
Validated questionnaire for anxiety.
Hospital Anxiety and Depression Scale (HADS)
Validated questionnaire for anxiety and depression.
Audiometry
pure-tone and speech audiometry. These are the clinical standard audiometric tests.
Auditory Brainstem Response
Neurophysiological measure following standard protocols.
Electroencephalography (EEG)
Neurophysiological measure following standard protocols.
Local Field Potentials (LFP)
Neurophysiological measure following standard protocols.

Full Information

First Posted
March 7, 2019
Last Updated
August 2, 2022
Sponsor
Maastricht University Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT03976908
Brief Title
Deep Brain Stimulation for Tinnitus
Official Title
Deep Brain Stimulation for Refractory Tinnitus
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 6, 2021 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Maastricht University Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tinnitus
Keywords
Tinnitus, Deep Brain Stimulation

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Model Description
Clinical intervention study (double blind, randomized cross-over design). Two different stimulation paradigms will be investigated: ON and OFF stimulation.
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
6 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
ON-OFF
Arm Type
Experimental
Arm Description
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.
Arm Title
OFF-ON
Arm Type
Experimental
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
Deep Brain Stimulation
Intervention Description
High frequency deep brain stimulation in the medial geniculate body of the thalamus.
Primary Outcome Measure Information:
Title
Change over time of the score on the Tinnitus Functional Index
Description
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.
Time Frame
Week 1, week 20, week 26, week 33, week 60
Secondary Outcome Measure Information:
Title
VAS Loudness
Description
on a scale from 0 (no tinnitus) to 10 (most severe tinnitus imaginable), subjects rate their tinnitus perception on loudness.
Time Frame
Week 1, week 12, week 20, week 26, week 33, week 60
Title
VAS Burden
Description
on a scale from 0 (no tinnitus) to 10 (most severe tinnitus imaginable), subjects rate their tinnitus perception amount of discomfort.
Time Frame
Week 1, week 12, week 20, week 26, week 33, week 60
Title
15 word memory test
Description
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.
Time Frame
Week 1, week 27, week 34, week 60
Title
Boston naming test
Description
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.
Time Frame
Week 1, week 27, week 34, week 60
Title
Stroop Color and Word Test
Description
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.
Time Frame
Week 1, week 27, week 34, week 60
Title
Trail Making Test
Description
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.
Time Frame
Week 1, week 27, week 34, week 60
Title
Semantic Verbal Fluency Test (Animals)
Description
This is a test in which participants have to produce as many words as possible from a category, here animals.
Time Frame
Week 1, week 27, week 34, week 60
Title
Semantic Verbal Fluency Test (Jobs)
Description
This is a test in which participants have to produce as many words as possible from a category, here jobs.
Time Frame
Week 1, week 27, week 34, week 60
Title
Phonemic Verbal Fluency Test (D)
Description
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.
Time Frame
Week 1, week 27, week 34, week 60
Title
Phonemic Verbal Fluency Test (A)
Description
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.
Time Frame
Week 1, week 27, week 34, week 60
Title
Phonemic Verbal Fluency Test (T)
Description
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.
Time Frame
Week 1, week 27, week 34, week 60
Title
Quality of life Questionnaire
Description
The Short Form (36) Health Survey (standard validated questionnaire)
Time Frame
Week 1, week 27, week 34, week 60
Title
Beck Depression Inventory II (BDI-II)
Description
Validated questionnaire for depression.
Time Frame
Week 1, week 60
Title
Beck Anxiety Inventory (BAI)
Description
Validated questionnaire for anxiety.
Time Frame
Week 1, week 60
Title
Hospital Anxiety and Depression Scale (HADS)
Description
Validated questionnaire for anxiety and depression.
Time Frame
Week 1, week 60
Title
Audiometry
Description
pure-tone and speech audiometry. These are the clinical standard audiometric tests.
Time Frame
Week 1, week 14, week 27, week 34, week 60
Title
Auditory Brainstem Response
Description
Neurophysiological measure following standard protocols.
Time Frame
Week 1, week 14, week 27, week 34, week 60
Title
Electroencephalography (EEG)
Description
Neurophysiological measure following standard protocols.
Time Frame
Week 1, week 14, week 27, week 34, week 60
Title
Local Field Potentials (LFP)
Description
Neurophysiological measure following standard protocols.
Time Frame
Week 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
69 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jana Devos, Drs.
Phone
+31644936611
Email
jana.devos@maastrichtuniversity.nl
First Name & Middle Initial & Last Name or Official Title & Degree
Jasper Smit, Dr.
Email
jasper.smit@maastrichtuniversiy.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark Janssen, Dr.
Organizational Affiliation
Maastricht University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
MUMC+
City
Maastricht
ZIP/Postal Code
6229HX
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jana VP Devos, Msc.
Email
jana.devos@maastrichtuniversity.nl
First Name & Middle Initial & Last Name & Degree
Jana VP Devos, Msc.
First Name & Middle Initial & Last Name & Degree
Marcus LF Janssen, Dr. MD.

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Deep Brain Stimulation for Tinnitus

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