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Evaluation of Deep Brain Stimulation (DBS) of the Right Operculum 3 (OP3) in Permanent Non-pulsatile Disabling Tinnitus (TINNOP3-DBS) (TINNOP3-DBS)

Primary Purpose

Severe Permanent Uni or Bilateral Non-pulsatile Tinnitus, Without Associated Vestibular Pathology, Resistant to Therapeutic Failure

Status
Recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
DBS
Sponsored by
University Hospital, Grenoble
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Severe Permanent Uni or Bilateral Non-pulsatile Tinnitus focused on measuring Tinnitus, Deep Brain Stimulation (DBS), Right operculum 3 (OP3), Functional Magnetic Resonance Imaging (fMRI), Magnetoencephalography (MEG), Local Field Potential (LFP), Visual Analog Scale (VAS), Tinnitus Handicap Inventory (THI) questionnaire, Hospital Anxiety and Depression Scale (HAD), Cross-over study, Double blind design

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Between 18 and 75 years old,
  2. Uni or bilateral permanent non-pulsatile tinnitus, without associated vestibular pathology, with or without hearing loss,
  3. Severe tinnitus resistant to treatment failure,
  4. Tinnitus intensity on the Visual Analog Scale (VAS) ≥ 7,
  5. Presenting a quality of life score on the Tinnitus Handicap Inventory (THI) questionnaire> 76 (= grade 5),
  6. Social security affiliates or beneficiaries of such a scheme
  7. Informed and written consent signed by the patient.

Exclusion Criteria:

  1. Vestibular dysfunction (balance disorder),
  2. Epilepsy,
  3. Intercurrent serious pathology,
  4. Brain tumor,
  5. Contraindication to surgery or anesthesia,
  6. History of cerebral infection with herpesvirus,
  7. With a contraindication to the practice of MRI, MEG, Computerized Tomography (CT) scan,
  8. Under anticoagulants and antiaggregants (Anti vitamin K, low molecular weight heparin, aspirin and derivatives, clopidogrel antiplatelet agents and assimilated, new oral anticoagulants (NACO)) for which a therapeutic window can not be opened within 3 months before and after the surgery,
  9. Included in another therapeutic protocol,
  10. Progressive dementia or psychiatric illness,
  11. Presenting a suicidal risk deemed important for less than 3 months (Montgomery and Asberg depression scale (MADRS): suicidality item (item 10) score> 2),
  12. Enforced hospitalisation,
  13. Pregnant, parturient or breastfeeding, lack of contraception in patients with the capacity to procreate,
  14. Subject to a legal protection measure,
  15. Deprived of liberty by judicial or administrative decision,
  16. Isolated patient without any contact in case of emergency.

Sites / Locations

  • CLINATECRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

Deep Brain Stimulation (DBS) activated

Deep Brain Stimulation (DBS) non-activated

Arm Description

Patients with severe permanent non-pulsatile tinnitus treated by Deep Brain Stimulation (DBS) in position ON

Patients with severe permanent non-pulsatile tinnitus treated by Deep Brain Stimulation (DBS) in position OFF

Outcomes

Primary Outcome Measures

Effectiveness of the treatment using Deep Brain Stimulation (DBS) of the right operculum 3 (OP3).
Difference in intensity of tinnitus Visual Analog Scale (VAS) [0/10 : higher scores mean better outcome] between the end and the beginning of each of the two periods of the crossover.

Secondary Outcome Measures

Incidence of DBS Treatment on Emergent Adverse Events (Tolerance) after surgical intervention and stimulation following the implantation of the DBS medical device.
Emergent Adverse events (partial or general epileptic seizures, worsening of tinnitus, surgical complications, ...): 1) post-operative computed tomography (CT); 2) Clinical evaluation.
Evaluation of the subjective effect of stimulation on quality of life.
Scores on the Tinnitus Handicap Inventory (THI) questionnaire [0/100 : higher scores mean worse outcome] at 6 months (early phase) and at 15 months compared to the preoperative THI of the same patient.
Evaluation of the subjective effect of stimulation on anxiety / depression.
Scores on the Hospital Anxiety and Depression Scale (HAD) [0/21 : higher scores mean worse outcome] at 6 months (early phase) and at 15 months compared to preoperative HAD of the same patient.
Changes comparison of the connectivity of OP3 explored by functional Magnetic Resonance Imaging (fMRI) at 1.5 T.
Functional Magnetic Resonance Imaging records (fMRI 1.5 T) performed preoperatively and at 15 months postoperatively.
Connectivities changes of the right OP3 measured by magnetoencephalography (MEG) at baseline 'preoperatively) and the post op (within 1 week) and at long term follow up (15 months) with active stimulation (ON) and inactive (OFF) during MEG recording.
Magnetoencephalography (MEG) records at baseline (preoperatively) and the post op (within 1 week) and at long term follow up (15 months) with active stimulation (ON) and inactive (OFF) during MEG recording.
Characterization of the Local Field Potential (LFP) recorded and correlations with tinnitus features perceived by the patient, based on their intensity and characteristic.
Local Field Potential (LFP) records on the electrode when the patient perceives tinnitus features 1) intraoperatively 2) before the implantation of the stimulator.

Full Information

First Posted
February 24, 2020
Last Updated
May 9, 2023
Sponsor
University Hospital, Grenoble
Collaborators
Commissariat A L'energie Atomique, Équipe 5 Neuroimagerie et perfusion cérébrale, Grenoble Institut des Neurosciences (GIN)
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1. Study Identification

Unique Protocol Identification Number
NCT04296097
Brief Title
Evaluation of Deep Brain Stimulation (DBS) of the Right Operculum 3 (OP3) in Permanent Non-pulsatile Disabling Tinnitus (TINNOP3-DBS)
Acronym
TINNOP3-DBS
Official Title
Evaluation of Deep Brain Stimulation (DBS) of the Right Operculum 3 (OP3) in Permanent Non-pulsatile Disabling Tinnitus (TINNOP3-DBS)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 23, 2021 (Actual)
Primary Completion Date
November 2023 (Anticipated)
Study Completion Date
February 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Grenoble
Collaborators
Commissariat A L'energie Atomique, Équipe 5 Neuroimagerie et perfusion cérébrale, Grenoble Institut des Neurosciences (GIN)

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
This pilot study aims at evaluating the effectiveness of the treatment of unilateral or bilateral, non-pulsatile, disabling, tinnitus, without vestibular dysfunction, using Deep Brain Stimulation (DBS) of the parieto-insular right operculum 3 (OP3) in a cross-over, double study design.
Detailed Description
Subjective, non-pulsatile, permanent, severe, tinnitus, refractory to all treatment are very disabling. They can lead to serious depression and suicidal behavior, which justifies the development of innovative therapeutic options. Current management is essentially based on psychological therapy and / or prosthetic, to improve for hearing loss that can be frequently associated. In fact, the main objective is habituation for these patients, but when the tinnitus is too intense, it is impossible. Three recent publications in functional magnetic resonance imaging (fMRI) have reported a novel physiopathological hypothesis to explain the appearance of subjective tinnitus. They highlight the prominent role of the right operculum 3 (OP3), a deep opercular region (parieto-insular junction) in the emergence of this symptom. The investigators hypothesize that inhibition of this region using high frequency stimulation could, significantly improve the intensity of the symptom and consequently their quality of life in this selected population.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Permanent Uni or Bilateral Non-pulsatile Tinnitus, Without Associated Vestibular Pathology, Resistant to Therapeutic Failure, With or Without Hearing Loss
Keywords
Tinnitus, Deep Brain Stimulation (DBS), Right operculum 3 (OP3), Functional Magnetic Resonance Imaging (fMRI), Magnetoencephalography (MEG), Local Field Potential (LFP), Visual Analog Scale (VAS), Tinnitus Handicap Inventory (THI) questionnaire, Hospital Anxiety and Depression Scale (HAD), Cross-over study, Double blind design

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Model Description
Deep Brain Stimulation (DBS) of the parieto-insular region at the level of the right operculum 3 (OP3)
Masking
ParticipantInvestigator
Masking Description
Crossover study conducted in double blind design : one month Deep Brain Stimulation (DBS) ON, 15 days wash out stimulation OFF, and one month Deep Brain Stimulation (DBS) OFF or one month Deep Brain Stimulation (DBS) OFF, 15 days wash out stimulation OFF, and one month Deep Brain Stimulation (DBS) ON
Allocation
Randomized
Enrollment
7 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Deep Brain Stimulation (DBS) activated
Arm Type
Experimental
Arm Description
Patients with severe permanent non-pulsatile tinnitus treated by Deep Brain Stimulation (DBS) in position ON
Arm Title
Deep Brain Stimulation (DBS) non-activated
Arm Type
Other
Arm Description
Patients with severe permanent non-pulsatile tinnitus treated by Deep Brain Stimulation (DBS) in position OFF
Intervention Type
Device
Intervention Name(s)
DBS
Intervention Description
Deep Brain Stimulation (DBS) of the parieto-insular region at the level of the right operculum 3 (OP3)
Primary Outcome Measure Information:
Title
Effectiveness of the treatment using Deep Brain Stimulation (DBS) of the right operculum 3 (OP3).
Description
Difference in intensity of tinnitus Visual Analog Scale (VAS) [0/10 : higher scores mean better outcome] between the end and the beginning of each of the two periods of the crossover.
Time Frame
2.5 months
Secondary Outcome Measure Information:
Title
Incidence of DBS Treatment on Emergent Adverse Events (Tolerance) after surgical intervention and stimulation following the implantation of the DBS medical device.
Description
Emergent Adverse events (partial or general epileptic seizures, worsening of tinnitus, surgical complications, ...): 1) post-operative computed tomography (CT); 2) Clinical evaluation.
Time Frame
15 months
Title
Evaluation of the subjective effect of stimulation on quality of life.
Description
Scores on the Tinnitus Handicap Inventory (THI) questionnaire [0/100 : higher scores mean worse outcome] at 6 months (early phase) and at 15 months compared to the preoperative THI of the same patient.
Time Frame
15 months
Title
Evaluation of the subjective effect of stimulation on anxiety / depression.
Description
Scores on the Hospital Anxiety and Depression Scale (HAD) [0/21 : higher scores mean worse outcome] at 6 months (early phase) and at 15 months compared to preoperative HAD of the same patient.
Time Frame
15 months
Title
Changes comparison of the connectivity of OP3 explored by functional Magnetic Resonance Imaging (fMRI) at 1.5 T.
Description
Functional Magnetic Resonance Imaging records (fMRI 1.5 T) performed preoperatively and at 15 months postoperatively.
Time Frame
15 months
Title
Connectivities changes of the right OP3 measured by magnetoencephalography (MEG) at baseline 'preoperatively) and the post op (within 1 week) and at long term follow up (15 months) with active stimulation (ON) and inactive (OFF) during MEG recording.
Description
Magnetoencephalography (MEG) records at baseline (preoperatively) and the post op (within 1 week) and at long term follow up (15 months) with active stimulation (ON) and inactive (OFF) during MEG recording.
Time Frame
15 months
Title
Characterization of the Local Field Potential (LFP) recorded and correlations with tinnitus features perceived by the patient, based on their intensity and characteristic.
Description
Local Field Potential (LFP) records on the electrode when the patient perceives tinnitus features 1) intraoperatively 2) before the implantation of the stimulator.
Time Frame
One week

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Between 18 and 75 years old, Uni or bilateral permanent non-pulsatile tinnitus, without associated vestibular pathology, with or without hearing loss, Severe tinnitus resistant to treatment failure, Tinnitus intensity on the Visual Analog Scale (VAS) ≥ 7, Presenting a quality of life score on the Tinnitus Handicap Inventory (THI) questionnaire> 76 (= grade 5), Social security affiliates or beneficiaries of such a scheme Informed and written consent signed by the patient. Exclusion Criteria: Vestibular dysfunction (balance disorder), Epilepsy, Intercurrent serious pathology, Brain tumor, Contraindication to surgery or anesthesia, History of cerebral infection with herpesvirus, With a contraindication to the practice of MRI, MEG, Computerized Tomography (CT) scan, Under anticoagulants and antiaggregants (Anti vitamin K, low molecular weight heparin, aspirin and derivatives, clopidogrel antiplatelet agents and assimilated, new oral anticoagulants (NACO)) for which a therapeutic window can not be opened within 3 months before and after the surgery, Included in another therapeutic protocol, Progressive dementia or psychiatric illness, Presenting a suicidal risk deemed important for less than 3 months (Montgomery and Asberg depression scale (MADRS): suicidality item (item 10) score> 2), Enforced hospitalisation, Pregnant, parturient or breastfeeding, lack of contraception in patients with the capacity to procreate, Subject to a legal protection measure, Deprived of liberty by judicial or administrative decision, Isolated patient without any contact in case of emergency.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Stéphan CHABARDES, MD, PhD
Phone
33 (0)4 76 76 93 85
Email
SChabardes@chu-grenoble.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Caroline SANDRE-BALLESTER, PhD
Phone
33 (0)4 38 78 28 51
Email
CSandreballester@chu-grenoble.fr
Facility Information:
Facility Name
CLINATEC
City
Grenoble
ZIP/Postal Code
38000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stephan CHABARDES, MD, PhD
Phone
33 (0)4 76 76 93 85
Email
SChabardes@chu-grenoble.fr
First Name & Middle Initial & Last Name & Degree
Caroline SANDRE-BALLESTER, PhD
Phone
33 (0)4 38 78 28 51
Email
CSandreballester@chu-grenoble.fr
First Name & Middle Initial & Last Name & Degree
Eric SEIGNEURET, MD, PhD

12. IPD Sharing Statement

Citations:
PubMed Identifier
21484948
Citation
Job A, Paucod JC, O'Beirne GA, Delon-Martin C. Cortical representation of tympanic membrane movements due to pressure variation: an fMRI study. Hum Brain Mapp. 2011 May;32(5):744-9. doi: 10.1002/hbm.21063.
Results Reference
background
PubMed Identifier
22574285
Citation
Job A, Pons Y, Lamalle L, Jaillard A, Buck K, Segebarth C, Delon-Martin C. Abnormal cortical sensorimotor activity during "Target" sound detection in subjects with acute acoustic trauma sequelae: an fMRI study. Brain Behav. 2012 Mar;2(2):187-99. doi: 10.1002/brb3.21.
Results Reference
background
PubMed Identifier
25503643
Citation
Job A, Jacob R, Pons Y, Raynal M, Kossowski M, Gauthier J, Lombard B, Delon-Martin C. Specific activation of operculum 3 (OP3) brain region during provoked tinnitus-related phantom auditory perceptions in humans. Brain Struct Funct. 2016 Mar;221(2):913-22. doi: 10.1007/s00429-014-0944-0. Epub 2014 Dec 12.
Results Reference
background
PubMed Identifier
17032710
Citation
Eickhoff SB, Grefkes C, Zilles K, Fink GR. The somatotopic organization of cytoarchitectonic areas on the human parietal operculum. Cereb Cortex. 2007 Aug;17(8):1800-11. doi: 10.1093/cercor/bhl090. Epub 2006 Oct 10.
Results Reference
background
PubMed Identifier
30414541
Citation
Maliia MD, Donos C, Barborica A, Popa I, Ciurea J, Cinatti S, Mindruta I. Functional mapping and effective connectivity of the human operculum. Cortex. 2018 Dec;109:303-321. doi: 10.1016/j.cortex.2018.08.024. Epub 2018 Sep 10.
Results Reference
background

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Evaluation of Deep Brain Stimulation (DBS) of the Right Operculum 3 (OP3) in Permanent Non-pulsatile Disabling Tinnitus (TINNOP3-DBS)

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