Clinical trial NCT04551404: Transcranial Electrical and Acoustic Stimulation for Tinnitus
Official title: Transcranial Electrical and Acoustic Stimulation for Tinnitus: A Randomized Double Blind Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Tinnitus
Tinnitus, Subjective
Lead sponsor: University of Zurich
Sponsor class: OTHER
First posted: 2020-09-16
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Male and female patients 18 years to 75 years of age (younger age limit according to corona virus protection concepts and measures of the FOPH: Schutzkonzepte und -massnahmen (admin.ch))
* Persistent chronic tinnitus with duration of more than 3 months
* Signed Informed Consent after being informed about the study
* Fluent in German or English
* 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

Primary outcomes:
measure: Change of self-report Visual Analogue Scale (VAS) ratings on tinnitus severity (loudness, distress)
timeFrame: up to 6 months
measure: Change of minimum masking level (MML)
timeFrame: up to 6 months
Secondary outcomes:
measure: event-related EEG power in alpha band
timeFrame: up to 6 months
Other outcomes:
Locations:
city: Zurich
country: Switzerland
facility: University Hospital Zurich, University Zurich
Study officials:
References:
citation: Antal A, Herrmann CS. Transcranial Alternating Current and Random Noise Stimulation: Possible Mechanisms. Neural Plast. 2016;2016:3616807. doi: 10.1155/2016/3616807. Epub 2016 May 3.
citation: Claes L, Stamberger H, Van de Heyning P, De Ridder D, Vanneste S. Auditory cortex tACS and tRNS for tinnitus: single versus multiple sessions. Neural Plast. 2014;2014:436713. doi: 10.1155/2014/436713. Epub 2014 Dec 22.
citation: Joos K, De Ridder D, Vanneste S. The differential effect of low- versus high-frequency random noise stimulation in the treatment of tinnitus. Exp Brain Res. 2015 May;233(5):1433-40. doi: 10.1007/s00221-015-4217-9. Epub 2015 Feb 19.
citation: Kreuzer PM, Poeppl TB, Rupprecht R, Vielsmeier V, Lehner A, Langguth B, Schecklmann M. Daily high-frequency transcranial random noise stimulation of bilateral temporal cortex in chronic tinnitus - a pilot study. Sci Rep. 2019 Aug 22;9(1):12274. doi: 10.1038/s41598-019-48686-0.
citation: Lee HY, Choi MS, Chang DS, Cho CS. Combined Bifrontal Transcranial Direct Current Stimulation and Tailor-Made Notched Music Training in Chronic Tinnitus. J Audiol Otol. 2017 Apr;21(1):22-27. doi: 10.7874/jao.2017.21.1.22. Epub 2017 Mar 30.
citation: Mohsen S, Mahmoudian S, Talebian S, Pourbakht A. Prefrontal and auditory tRNS in sequence for treating chronic tinnitus: a modified multisite protocol. Brain Stimul. 2018 Sep-Oct;11(5):1177-1179. doi: 10.1016/j.brs.2018.04.018. Epub 2018 Apr 25. No abstract available.
citation: Rabau S, Van Rompaey V, Van de Heyning P. The effect of Transcranial Direct Current Stimulation in addition to Tinnitus Retraining Therapy for treatment of chronic tinnitus patients: a study protocol for a double-blind controlled randomised trial. Trials. 2015 Nov 10;16:514. doi: 10.1186/s13063-015-1041-2.
citation: Shekhawat GS, Kobayashi K, Searchfield GD. Methodology for studying the transient effects of transcranial direct current stimulation combined with auditory residual inhibition on tinnitus. J Neurosci Methods. 2015 Jan 15;239:28-33. doi: 10.1016/j.jneumeth.2014.09.025. Epub 2014 Oct 5.
citation: Teismann H, Wollbrink A, Okamoto H, Schlaug G, Rudack C, Pantev C. Combining transcranial direct current stimulation and tailor-made notched music training to decrease tinnitus-related distress--a pilot study. PLoS One. 2014 Feb 25;9(2):e89904. doi: 10.1371/journal.pone.0089904. eCollection 2014.
citation: Van Doren J, Langguth B, Schecklmann M. Electroencephalographic effects of transcranial random noise stimulation in the auditory cortex. Brain Stimul. 2014 Nov-Dec;7(6):807-12. doi: 10.1016/j.brs.2014.08.007. Epub 2014 Aug 26.
citation: Vanneste S, Fregni F, De Ridder D. Head-to-Head Comparison of Transcranial Random Noise Stimulation, Transcranial AC Stimulation, and Transcranial DC Stimulation for Tinnitus. Front Psychiatry. 2013 Dec 18;4:158. doi: 10.3389/fpsyt.2013.00158. eCollection 2013.
citation: Martins ML, Kleinjung T, Meyer M, Raveenthiran V, Wellauer Z, Peter N, Neff P. Transcranial electric and acoustic stimulation for tinnitus: study protocol for a randomized double-blind controlled trial assessing the influence of combined transcranial random noise and acoustic stimulation on tinnitus loudness and distress. Trials. 2022 May 19;23(1):418. doi: 10.1186/s13063-022-06253-5.