Resistant to Therapeutic Failure, Severe Permanent Uni or Bilateral Non-pulsatile Tinnitus, With or Without Hearing Loss, Without Associated Vestibular Pathology
Conditions
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
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.
Interventions
DEVICEDBS
Deep Brain Stimulation (DBS) of the parieto-insular region at the level of the right operculum 3 (OP3)
Sponsors
Commissariat A L'energie Atomique
Équipe 5 Neuroimagerie et perfusion cérébrale, Grenoble Institut des Neurosciences (GIN)
University Hospital, Grenoble
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
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
Intervention model description
Deep Brain Stimulation (DBS) of the parieto-insular region at the level of the right operculum 3 (OP3)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effectiveness of the treatment using Deep Brain Stimulation (DBS) of the right operculum 3 (OP3). | 2.5 months | 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
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of the subjective effect of stimulation on quality of life. | 15 months | 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. | 15 months | 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. |
| Incidence of DBS Treatment on Emergent Adverse Events (Tolerance) after surgical intervention and stimulation following the implantation of the DBS medical device. | 15 months | Emergent Adverse events (partial or general epileptic seizures, worsening of tinnitus, surgical complications, ...): 1) post-operative computed tomography (CT); 2) Clinical evaluation. |
| 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. | 15 months | 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. | One week | Local Field Potential (LFP) records on the electrode when the patient perceives tinnitus features 1) intraoperatively 2) before the implantation of the stimulator. |
| Changes comparison of the connectivity of OP3 explored by functional Magnetic Resonance Imaging (fMRI) at 1.5 T. | 15 months | Functional Magnetic Resonance Imaging records (fMRI 1.5 T) performed preoperatively and at 15 months postoperatively. |
Countries
France
Contacts
Primary ContactStéphan CHABARDES, MD, PhD
Backup ContactCaroline SANDRE-BALLESTER, PhD
Outcome results
None listed