Clinical trial NCT04296097: Evaluation of Deep Brain Stimulation (DBS) of the Right Operculum 3 (OP3) in Permanent Non-pulsatile Disabling Tinnitus (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
Overall status: RECRUITING
Phase: NA
Conditions: 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
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
Collaborators: name: Commissariat A L'energie Atomique
name: Équipe 5 Neuroimagerie et perfusion cérébrale, Grenoble Institut des Neurosciences (GIN)
First posted: 2020-03-05
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Deep Brain Stimulation (DBS) of the parieto-insular region at the level of the right operculum 3 (OP3)
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Effectiveness of the treatment using Deep Brain Stimulation (DBS) of the right operculum 3 (OP3).
timeFrame: 2.5 months
Secondary outcomes:
measure: Incidence of DBS Treatment on Emergent Adverse Events (Tolerance) after surgical intervention and stimulation following the implantation of the DBS medical device.
timeFrame: 15 months
measure: Evaluation of the subjective effect of stimulation on quality of life.
timeFrame: 15 months
measure: Evaluation of the subjective effect of stimulation on anxiety / depression.
timeFrame: 15 months
measure: Changes comparison of the connectivity of OP3 explored by functional Magnetic Resonance Imaging (fMRI) at 1.5 T.
timeFrame: 15 months
measure: 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.
timeFrame: 15 months
measure: Characterization of the Local Field Potential (LFP) recorded and correlations with tinnitus features perceived by the patient, based on their intensity and characteristic.
timeFrame: One week
Other outcomes:
Locations:
city: Grenoble
country: France
facility: CLINATEC
Study officials:
References:
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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.
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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.
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.