Transcranial Electrical and Acoustic Stimulation for Tinnitus

Study Overview
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Brief Summary
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Transcranial electrical stimulation (tES) is an umbrella term for non-invasive brain stimulation using weak currents. It comprises transcranial direct current stimulation (tDCS), which is the most established and used method applying constant direct current, transcranial alternating current stimulation (tACS) with sinusoidal current in a fixed frequency, and finally transcranial random noise stimulation (tRNS), which is a subform of tACS generating a random range of low and high frequency alternating currents. A pilot study conducted by Shekhawat and colleagues in 2015 tested the effects of simultaneous electrical and acoustic stimulation. Using tDCS and bilateral broadband noise simultaneously, they found that more tinnitus patients report an improvement in tinnitus perception in comparison to conditions only using tDCS or sham. Further similar approaches very published in recent years, namely a pilot study conducted by Teissmann et al in 2014; study protocols of Rabau et al. in 2015 and Shekhawat et al. in 2015; and an experimental study by Lee et al. in 2017. Results were indicative of a superior efficacy of combined electrical and acoustic approaches, while large-scale controlled studies have not been performed. The need for extension and replication of these approaches is therefore timely. The aim behind our proposed approach, similar to the bimodal approaches above, is to couple the effects of tRNS and acoustic stimulation (AS) for better temporary tinnitus suppression and possible reversal of maladaptive neuroplasticity related to tinnitus. We aim at targeting the (bilateral) auditory cortex with tRNS as in former studies and combine it with white noise (WN) stimulation. This specific combination is novel in its nature and is building on cortical excitability following tRNS.

Official Title
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Transcranial Electrical and Acoustic Stimulation for Tinnitus: A Randomized Double Blind Clinical Trial

Conditions
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Tinnitus, Tinnitus, Subjective

Intervention / Treatment
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* Other: transcranial Random Noise Stimulation (tRNS) with acoustic stimulation (AS)
* Other: transcranial Random Noise Stimulation (tRNS) without acoustic stimulation (AS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients 18 years to 75 years of age Persistent chronic tinnitus with duration of more than 3 months Signed Informed Consent after being informed about the study Fluent in German Tinnitus with a THI Grade 2 to 4 (18-76 points) Willing and able to attend the study visits Exclusion Criteria: Actual neurological or psychiatric disorders Hyperacusis Regular intake of medication influencing the central nervous system (e.g. neuroleptics, hypnotics, sedatives, and anti-epileptics) Implanted pacemaker Surgical implants in the head region, such as cochlea implants Asymmetrical hearing (more than 20dB side difference), pantonal hearing loss > 40dB in any measured frequency up to 2kHz Women who are pregnant or breast feeding Intention to become pregnant during the course of the study Known or suspected non-compliance, drug or alcohol abuse Participation in another study with investigational drug within the 30 days preceding and during the present study, Enrolment of the investigator, his/her family members, employees and other dependent persons

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: The crossover within-person design with 2 groups, 2 active conditions and appropriate control/pseudo-placebo/sham session is double-blinded. Overall, participants will undergo 20 stimulation visits and 6 additional assessment visits. Prior to conducting the above study, a pilot study of 40 patients and just 6 visits will be conducted to validate clinical procedures and outcomes. This procedure was approved by the ethics committee.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Intervention(s) A<br>TRNS bilateral temporal regions combined with AS for 20 minutes Sham-tRNS bilateral temporal regions combined with Sham-AS for 20 minutes | Other: transcranial Random Noise Stimulation (tRNS) with acoustic stimulation (AS)<br>* The study intervention consists of a bilateral tRNS application over temporal regions, parallel to the application of AS with WN 15 dB above the individual MML in one study arm. TRNS will be applied using two electrodes (35 qcm, 0,9% saline -soaked). Stimulus intensity will be below individual sensation threshold, but max. 2 mA. AS will never surpass 85 dB SPL at the ears.<br>|
| Experimental: Study Intervention(s) B = Control Intervention<br>TRNS bilateral temporal regions for 20 minutes Sham-tRNS bilateral temporal regions for 20 minutes | Other: transcranial Random Noise Stimulation (tRNS) without acoustic stimulation (AS)<br>* The study intervention consists of a bilateral tRNS application over temporal regions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of self-report Visual Analogue Scale (VAS) ratings on tinnitus severity (loudness, distress) | Minmum value = 1, maximum value =10. The higher scores means a worse outcome. | up to 6 months | 
| Change of minimum masking level (MML) |  | up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| event-related EEG power in alpha band | The influence of simultaneous tRNS and AS stimulation on neurophysiology will be investigated as a secondary outcome. Resting state and event-related EEG (auditory oddball) (Attias et al., 1993) will be recorded for that purpose. | up to 6 months |