PMID- 31553940 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240807 IS - 1933-0693 (Electronic) IS - 0022-3085 (Print) IS - 0022-3085 (Linking) VI - 133 IP - 4 DP - 2020 Oct 1 TI - Phase I trial of caudate deep brain stimulation for treatment-resistant tinnitus. PG - 992-1001 LID - 10.3171/2019.4.JNS19347 [doi] AB - OBJECTIVE: The objective of this open-label, nonrandomized trial was to evaluate the efficacy and safety of bilateral caudate nucleus deep brain stimulation (DBS) for treatment-resistant tinnitus. METHODS: Six participants underwent DBS electrode implantation. One participant was removed from the study for suicidality unrelated to brain stimulation. Participants underwent a stimulation optimization period that ranged from 5 to 13 months, during which the most promising stimulation parameters for tinnitus reduction for each individual were determined. These individual optimal stimulation parameters were then used during 24 weeks of continuous caudate stimulation to reach the endpoint. The primary outcome for efficacy was the Tinnitus Functional Index (TFI), and executive function (EF) safety was a composite z-score from multiple neuropsychological tests (EF score). The secondary outcome for efficacy was the Tinnitus Handicap Inventory (THI); for neuropsychiatric safety it was the Frontal Systems Behavior Scale (FrSBe), and for hearing safety it was pure tone audiometry at 0.5, 1, 2, 3, 4, and 6 kHz and word recognition score (WRS). Other monitored outcomes included surgery- and device-related adverse events (AEs). Five participants provided full analyzable data sets. Primary and secondary outcomes were based on differences in measurements between baseline and endpoint. RESULTS: The treatment effect size of caudate DBS for tinnitus was assessed by TFI [mean (SE), 23.3 (12.4)] and THI [30.8 (10.4)] scores, both of which were statistically significant (Wilcoxon signed-rank test, 1-tailed; alpha = 0.05). Based on clinically significant treatment response categorical analysis, there were 3 responders determined by TFI (>/= 13-point decrease) and 4 by THI (>/= 20-point decrease) scores. Safety outcomes according to EF score, FrSBe, audiometric thresholds, and WRS showed no significant change with continuous caudate stimulation. Surgery-related and device-related AEs were expected, transient, and reversible. There was only one serious AE, a suicide attempt unrelated to caudate neuromodulation in a participant in whom stimulation was in the off mode for 2 months prior to the event. CONCLUSIONS: Bilateral caudate nucleus neuromodulation by DBS for severe, refractory tinnitus in this phase I trial showed very encouraging results. Primary and secondary outcomes revealed a highly variable treatment effect size and 60%-80% treatment response rate for clinically significant benefit, and no safety concerns. The design of a phase II trial may benefit from targeting refinement for final DBS lead placement to decrease the duration of the stimulation optimization period and to increase treatment effect size uniformity.Clinical trial registration no.: NCT01988688 (clinicaltrials.gov). FAU - Cheung, Steven W AU - Cheung SW AD - 1Department of Otolaryngology-Head and Neck Surgery, UCSF. AD - 2Surgical Services, Veterans Affairs Health Care System, San Francisco. FAU - Racine, Caroline A AU - Racine CA AD - 3Department of Neurological Surgery, UCSF. FAU - Henderson-Sabes, Jennifer AU - Henderson-Sabes J AD - 1Department of Otolaryngology-Head and Neck Surgery, UCSF. FAU - Demopoulos, Carly AU - Demopoulos C AD - 4Department of Psychiatry, UCSF. AD - 5Department of Radiology and Biomedical Imaging, UCSF. FAU - Molinaro, Annette M AU - Molinaro AM AD - 3Department of Neurological Surgery, UCSF. FAU - Heath, Susan AU - Heath S AD - 2Surgical Services, Veterans Affairs Health Care System, San Francisco. FAU - Nagarajan, Srikantan S AU - Nagarajan SS AD - 1Department of Otolaryngology-Head and Neck Surgery, UCSF. AD - 5Department of Radiology and Biomedical Imaging, UCSF. FAU - Bourne, Andrea L AU - Bourne AL AD - 6Audiology and Speech Pathology Service, Veterans Affairs Health Care System, San Francisco; and. FAU - Rietcheck, John E AU - Rietcheck JE AD - 6Audiology and Speech Pathology Service, Veterans Affairs Health Care System, San Francisco; and. FAU - Wang, Sarah S AU - Wang SS AD - 7Department of Neurology, UCSF, San Francisco, California. FAU - Larson, Paul S AU - Larson PS AD - 2Surgical Services, Veterans Affairs Health Care System, San Francisco. AD - 3Department of Neurological Surgery, UCSF. LA - eng SI - ClinicalTrials.gov/NCT01988688 GR - K23 DC016637/DC/NIDCD NIH HHS/United States GR - U01 DC013029/DC/NIDCD NIH HHS/United States PT - Journal Article DEP - 20190924 PL - United States TA - J Neurosurg JT - Journal of neurosurgery JID - 0253357 SB - IM PMC - PMC7089839 MID - NIHMS1027124 OTO - NOTNLM OT - caudate nucleus OT - corticostriatal OT - deep brain stimulation OT - executive function OT - functional neurosurgery OT - phase I trial OT - tinnitus EDAT- 2019/09/26 06:00 MHDA- 2019/09/26 06:01 PMCR- 2021/03/24 CRDT- 2019/09/26 06:00 PHST- 2019/02/08 00:00 [received] PHST- 2019/04/11 00:00 [accepted] PHST- 2019/09/26 06:01 [medline] PHST- 2019/09/26 06:00 [pubmed] PHST- 2019/09/26 06:00 [entrez] PHST- 2021/03/24 00:00 [pmc-release] AID - 2019.4.JNS19347 [pii] AID - 10.3171/2019.4.JNS19347 [doi] PST - epublish SO - J Neurosurg. 2019 Sep 24;133(4):992-1001. doi: 10.3171/2019.4.JNS19347. Print 2020 Oct 1.