Exploring a novel brain stimulation protocol for treatment of tinnitus

INTERVENTION: high definition transcranial infraslow pink noise stimulation (HD‐tIPNS) will be administered by a researcher experienced in administering neuromodulation techniques. HD‐tIPNS will be administered face‐to‐face, three times a week for four weeks (i.e. total of 12 intervention sessions) in the Department of surgical sciences laboratory at the Dunedin School of Medicine, University of Otago. Each intervention session will have a duration of 1hr (30min set‐up and 30min of stimulation). For the active treatment group (HD‐tIPNS), the stimulation will be delivered at a current strength of maximum of 2mA for 30min, with 60s ramp up and ramp down at the beginning and end of each stimulation session, with continuous stimulation in between. The pink noise stimulation at a current strength of maximum of 0.6mA will be superimposed on the infraslow stimulation waveform of a current intensity of 1mA, such that the current strength of the waveform never exceeds the maximum of 2mA. For the sham stimulation group, to create an identical skin sensation to the active stimulation, the current will be applied for a 60s ramp up (0‐2mA) and 60s ramp down (2‐0mA), at the beginning and the end of each stimulation session, without any current for the remainder of the stimulation period. A battery‐driven wireless 32 channel transcranial current stimulation (Starstim32 TES®, Neuroelectrics, Spain, http://www.neuroelectrics.com) will be used to deliver stimulation while the participants are comfortably and quietly seated. The Starstim32 is a high definition system with small electrode size (1 cm radius) that can focally target deeper brain regions. Thirty‐two circular Ag/AgCl stimulation electrodes will be placed on a neoprene head cap following the International 10‐20 EEG system to target the AC, CONDITION: Ear ‐ Other ear disorders Neurological ‐ Other neurological disorders Tinnitus; ; Tinnitus PRIMARY OUTCOME: Change in participant perception of tinnitus' impact on their daily lives, measured using the mini tinnitus questionnaire (mTQ), [Baseline, immediately post‐intervention phase, and at 7 days after completion of the intervention phase.] change in resting‐state electroencephalography (EEG) activity as assessed by standard low‐resolution brain electromagnetic tomography (sLORETA)[Baseline, immediately post‐intervention phase, and at 7 days after completion of the intervention phase. ] Safety is a composite primary outcome, measured by the occurrence of any adverse event or reaction will be recorded on a case report form detailing a verbatim description of the event, intensity of each symptom using a likert scale ranging from 0 (none) to 10 (extreme), relation of the symptom to the treatment using a scale ranging from 1 (unrelated) to 5 (strongly related), duration of each symptom and time taken for each symptom to resolve (expressed in min), and any drop‐outs due to adverse effects.[At each session before the intervention, during the intervention (at 5min intervals), and after completion of the day’s intervention session] INCLUSION CRITERIA: Capable of understanding and signing an informed consent form A diagnosis of chronic tinnitus (> 2 years) At Screening, have constant subjective tinnitus with a grade of 3‐4 on the mTQ and a TFI score of 25 or greater (indicating moderate/severe presentation with significant problems associated with tinnitus) SECONDARY OUTCOME: An 11‐point numeric rating scale designed specifically for this study by the primary and coordinating investigators will be used to measure tinnitus loudness, suffering, unpleasantness, fear, frustration, anger, and association with self‐perception. This is an additional primary outcome measure.[Baseline, immediately post‐intervention phase, and at 7 days after completion of the intervention phase.] Change in tinnitus functional index (TFI) score will be used to assess tinnitus associated distress. This is an additional primary outcome measure.[Baseline, immediately post‐intervention phase, and at 7 days after completion of the intervention phase.] Depression, anxiety, and stress scale (DASS‐21) is a 21‐item questionnaire that will be used to assess changes in participant depression, anxiety and stress levels. This is an additional primary outcome measure. [Baseline, immediately post‐intervention phase, and at 7 days after completion of the intervention phase.] Number of participants recruited per month until sample size of 20 is reached, determined by an audit of the study database. [This will be assessed once recruitment has ended.] Participant satisfaction level and acceptability of the HD‐tIPNS will be assessed using an 11‐point numeric rating scale (0‐Not at all satisfied/acceptable to 10‐Very satisfied/acceptable).[Participant satisfaction and acceptability of HD‐tIPNS will be assessed once the 4‐week treatment phase is complete. ] Percentage of participants that drop‐out of the study will be determined by an audit of the study database. [Drop‐out rates will be calculated once the 1‐week follow‐up phase is completed (i.e. 5 weeks post‐intervention commencement). ] Percentage of treatment sessions attended (i.e. adherence rate) will be determined by an audit of the study database. [Adherence rate will be calculated once the 4‐week treatment phase is complete.] Proportion of participants recruited from the total number screened will be determined by an audit of the study database. [This will be assessed once recruitment has ended ] The European Quality of Life‐5 Dimensions (EQ‐5D) scale will be used to assess the health related quality of life for all participants. This is an additional primary outcome measure. [Baseline, immediately post‐intervention phase, and at 7 days after completion of the intervention phase.] The tinnitus catastrophizing scale (TCS) will be used to assess excessively negative misinterpretations of tinnitus. This is an additional primary outcome measure. [Baseline, immediately post‐intervention phase, and at 7 days after completion of the intervention phase.] The TrackYourTinnitus (TYT) app will be used by participants to record instances of their tinnitus, which will measure changes in frequency of tinnitus perception over time. This is an additional primary outcome measure.[Baseline, immediately post‐intervention phase, and at 7 days after completion of the intervention phase. ] The World health Organisation‐5 Well‐being Index (WHO‐5) consists of self‐reported 5‐items and will be used to assess current mental well‐being of all participants. This is an additional primary outcome measure.[Baseline, immediately post‐intervention phase, and at 7 days after completion of the intervention phase.]