Resistant to Therapeutic Failure Clinical Trial
— TINNOP3-DBSOfficial title:
Evaluation of Deep Brain Stimulation (DBS) of the Right Operculum 3 (OP3) in Permanent Non-pulsatile Disabling Tinnitus (TINNOP3-DBS)
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.
| Status | Recruiting |
| Enrollment | 7 |
| Est. completion date | October 2026 |
| Est. primary completion date | October 2026 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 75 Years |
| Eligibility | 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. |
| Country | Name | City | State |
|---|---|---|---|
| France | CLINATEC | Grenoble |
| Lead Sponsor | Collaborator |
|---|---|
| University Hospital, Grenoble | Commissariat A L'energie Atomique, Équipe 5 Neuroimagerie et perfusion cérébrale, Grenoble Institut des Neurosciences (GIN) |
France,
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. — View 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. — View 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. — View 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. — View 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. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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. | 2.5 months | |
| Secondary | 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. | 15 months | |
| Secondary | 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. | 15 months | |
| Secondary | 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. | 15 months | |
| Secondary | 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. | 15 months | |
| Secondary | 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. | 15 months | |
| Secondary | 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. | One week |