Clinical trial NCT06083519: Assessment of a Novel Sound-based Treatment for Managing Distress Related to Tinnitus
Official title: Assessment of a Novel Sound-based Treatment for Managing Distress Related to Tinnitus
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Tinnitus
Keywords: tinnitus
iso principle
artificial intelligence
auditory perception
sound therapy
neuroscience
neuromodulatory intervention
auditory beat stimulation
Lead sponsor: Toronto Metropolitan University
Sponsor class: OTHER
Collaborators: name: Lucid, Inc.
name: Sonova Canada Inc.
name: Mitacs
First posted: 2023-10-16
Enrollment: 50
Sex: ALL
Minimum age (years): 50
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: SUPPORTIVE_CARE

Brief summary: The goal of this clinical trial is to assess the effectiveness of a sound-based passive treatment for reducing stress and annoyance induced by tinnitus, and how this therapy may improve tinnitus sufferers' quality of life. The main questions it aims to answer are: • \[question 1: to assess the efficacy of the LUCID/VIBE in managing the tinnitus handicap (measured by the reducing of the annoyance/stress response to tinnitus) contributing to the improvement of the quality of life of people living with tinnitus\] and • \[question 2: assess the efficacy of LUCID/VIBE in providing temporary relief through masking, such that it results in a reduction of the perceived loudness of tinnitus\]. Participants will \[use the VIBE app for 24 minutes a day for a period of 4 weeks. There will be two conditions, a Noise condition (the control condition in which the investigator will administer white noise) and the VIBE condition (the treatment condition). One approach involves broad-band masking with noise (Noise Condition), while the other uses music (LUCID Condition). Implementation of the noise condition will mirror the LUCID condition in terms of ease of access, look, feel, so that one condition does not look less professional than the other. Both conditions will be administered through the same app, and only the sound conditions will differ (white noise vs. LUCID music). All participants will be exposed to both the treatment and control conditions with the order of conditions counter-balanced (i.e., a cross-over design).

Detailed description: The current LUCID approach utilizes the VIBE app to help provide a mask for tinnitus, manage the distress related to tinnitus, and potentially dampen stress reactivity when used regularly due to the increase in parasympathetic activity. Previous findings have demonstrated that chronic tinnitus patients have elevated stress reactivity. There has also been evidence to suggest that regular music therapy interventions may enhance parasympathetic activity in the autonomic nervous system. In the past, LUCID has advanced approaches in Artificial Intelligence technology, psychology, and neuroscience to explore the potential of music to improve health and well-being. Their work to date has focused on mental health indications related to stress and anxiety. This current study differs from their previous projects because of its exploration of tinnitus rather than stress and anxiety. Their customer-facing developments have been focused on an application programming interface that has been integrated by digital-health partners and a consumer-facing app (VIBE) that has been used to support research and development. The VIBE app (LUCID) incorporates theta-band (4 Hz) auditory beat stimulation and an auditory music recommendation system. The additive effect of these elements in the treatment of acute anxiety in individuals living with moderate trait anxiety was recently demonstrated in a randomized clinical trial.

The automated music recommendation system developed by LUCID employs the iso principle along with affective classification and reinforcement learning to cultivate affect-driven personalized music sequences. The iso principal is a methodology used in music therapy to achieve mood induction that involves matching musical stimuli to a patient's current mood and gradually changing the music in the direction of their desired mood state. The iso principle has been indicated in prior research to be more effective than other musical sequences at reducing tension. The system requires that a user input their current mood using the arousal and valence dimensions of the Russell Circumplex Model. Based on this input as well as the target emotional state of calm, the machine learning algorithm within the application predicts the optimal sequence of tracks to produce mood induction in the listener from their current emotional state to the target state. This machine learning algorithm uses reinforcement learning techniques and is trained on real-world data correlating the quantitative features of musical excerpts and sequences alongside the emotional responses induced by them in listeners.

For this study. there will be two groups with 25 participants per group. For the control condition, a white-noise treatment for the noise condition will be administered. The researchers will be using an open-label randomized controlled trial study where the participants are told that the researchers are attempting to assess the effectiveness of two common interventions for tinnitus. One approach involves broad-band masking with noise (Noise Condition), while the other uses music (LUCID Condition). Implementation of the noise condition will mirror the LUCID condition in terms of ease of access, look, feel, so that one condition does not look less professional than the other. Both conditions will be administered through the same app, and only the sound conditions will differ (white noise vs. LUCID music). All participants will be exposed to both the treatment and control conditions with the order of conditions counter-balanced (i.e., a cross-over design). The LUCID treatment will be compared to the active control across 50 people. The participant is expected to engage in daily use of VIBE app at a specified time (e.g., for 24 minutes daily) and as needed to help mask symptoms of tinnitus. To minimize variability in dosage across groups, the investigators will impose daily limits and minimum adherence standards. Participants will be permitted to use the app for a maximum of 48 minutes per day (i.e., 200% of recommended dosage). Participants who use the app greater than 60 minutes (250% of recommended dosage) or less than 12 minutes per day on average (50% of recommended dosage) or who use the app on less than 75% of the trial days will be considered non-adherent and will be removed from the final sample subjected to analyses. These types of adherence boundaries are typical for decentralized clinical trials involving digital therapeutics. The VIBE app will be deployed on the participant's smartphone, and they will be instructed to use their own headphones (i.e., there is no standardization of the playback system). The app has built-in features which allow us to assess adherence to treatment. Participants in the study will experience each intervention condition for a period of 4 weeks. It is encouraged that the participants stop the study if they believe the sound therapy is exacerbating their tinnitus, their reaction to tinnitus, or negatively affecting their hearing ability.

Eligibility criteria: Inclusion Criteria:

* Pure-Tone Average hearing loss (500, 1000, 2000, 4000) of 30 decibels hearing loss or greater in the better ear.
* Tinnitus Handicap Index scores of 18 to 76 (mild to severe handicap).
* Self-report of chronic, non-intermittent tinnitus experienced \> 3 months

Exclusion Criteria:

* Adults younger than 50 years old, or adults older than 80 years old.
* Pulsatile tinnitus (tinnitus that modulates synchronously with a participant's pulse)
* \>20 dB HL difference in pure-tone average between ears
* \> 80 dB HL PTA averaged across ears
* Individuals currently undergoing other tinnitus treatment programs will not be able to participate in our study. This is to ensure that our findings are accurately attributed to our App and not influenced by external factors. If someone is already receiving treatment for their tinnitus, it would be challenging to distinguish the effects of our App from their existing treatment regimen. To eliminate the possibility of such confounding factors, our team kindly asks participants to disclose if they are undergoing other treatments for tinnitus.

Primary outcomes:
measure: Tinnitus Functional Index
timeFrame: The questionnaire is administered up to two weeks pre-intervention, and again up to two weeks post-intervention measure. The measurements will be compared to see if the intervention created a change.
measure: 36-item Short Form Health Survey
timeFrame: The questionnaire is administered up to two weeks pre-intervention, and again up to two weeks post-intervention measure. The measurements will be compared to see if the intervention created a change.
Secondary outcomes:
measure: Visual Analogue System
timeFrame: Up to 48 hours after each usage.
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Toronto Metropolitan University
state: Ontario
Study officials:
affiliation: Toronto Metropolitan University
name: Brandon Paul, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Aazh H, Salvi R. The Relationship between Severity of Hearing Loss and Subjective Tinnitus Loudness among Patients Seen in a Specialist Tinnitus and Hyperacusis Therapy Clinic in UK. J Am Acad Audiol. 2019 Sep;30(8):712-719. doi: 10.3766/jaaa.17144. Epub 2018 Nov 8.
citation: Garcia-Argibay M, Santed MA, Reales JM. Efficacy of binaural auditory beats in cognition, anxiety, and pain perception: a meta-analysis. Psychol Res. 2019 Mar;83(2):357-372. doi: 10.1007/s00426-018-1066-8. Epub 2018 Aug 2.
citation: Gopinath B, McMahon CM, Rochtchina E, Karpa MJ, Mitchell P. Risk factors and impacts of incident tinnitus in older adults. Ann Epidemiol. 2010 Feb;20(2):129-35. doi: 10.1016/j.annepidem.2009.09.002.
citation: Hall DA, Haider H, Szczepek AJ, Lau P, Rabau S, Jones-Diette J, Londero A, Edvall NK, Cederroth CR, Mielczarek M, Fuller T, Batuecas-Caletrio A, Brueggemen P, Thompson DM, Norena A, Cima RF, Mehta RL, Mazurek B. Systematic review of outcome domains and instruments used in clinical trials of tinnitus treatments in adults. Trials. 2016 Jun 1;17(1):270. doi: 10.1186/s13063-016-1399-9.
citation: Hullfish J, Sedley W, Vanneste S. Prediction and perception: Insights for (and from) tinnitus. Neurosci Biobehav Rev. 2019 Jul;102:1-12. doi: 10.1016/j.neubiorev.2019.04.008. Epub 2019 Apr 15.
citation: Mallik A, Russo FA. The effects of music & auditory beat stimulation on anxiety: A randomized clinical trial. PLoS One. 2022 Mar 9;17(3):e0259312. doi: 10.1371/journal.pone.0259312. eCollection 2022.
citation: McConnell PA, Froeliger B, Garland EL, Ives JC, Sforzo GA. Auditory driving of the autonomic nervous system: Listening to theta-frequency binaural beats post-exercise increases parasympathetic activation and sympathetic withdrawal. Front Psychol. 2014 Nov 14;5:1248. doi: 10.3389/fpsyg.2014.01248. eCollection 2014.
citation: Nondahl DM, Cruickshanks KJ, Dalton DS, Klein BE, Klein R, Schubert CR, Tweed TS, Wiley TL. The impact of tinnitus on quality of life in older adults. J Am Acad Audiol. 2007 Mar;18(3):257-66. doi: 10.3766/jaaa.18.3.7.
citation: Zhang Y, Qu B, Lun SS, Guo Y, Liu J. The 36-item short form health survey: reliability and validity in Chinese medical students. Int J Med Sci. 2012;9(7):521-6. doi: 10.7150/ijms.4503. Epub 2012 Aug 27.
citation: Rider, M. S. (1985). Entrainment mechanisms are involved in pain reduction, muscle relaxation, and musicmediated imagery. Journal of Music Therapy, 22(4), 183-92. doi: 10.1093/jmt/22.4.183.
citation: Heiderscheit, A., Madson, A. (2015). Use of the iso principle as a central method in mood management: A music psychotherapy clinical case study. Music Therapy Perspectives, 33(1), 45-52.
citation: Labbé A, McMahon, Z., & Thomson, Z. (2021). Music as Medicine: LUCID Science + Technology White Paper. [White Paper]. Available online at https://uploads ssl.webflow.com/60b8a3f8bd91d547f8a453dc/614e1cead49a3cadb1880924_Whitepaper%20- %20Public-Facing.pdf
citation: Remmington NA, Fabrigar LR, Visser PS. Reexamining the circumplex model of affect. J Pers Soc Psychol. 2000 Aug;79(2):286-300. doi: 10.1037//0022-3514.79.2.286.
citation: Sindhusake D, Golding M, Newall P, Rubin G, Jakobsen K, Mitchell P. Risk factors for tinnitus in a population of older adults: the blue mountains hearing study. Ear Hear. 2003 Dec;24(6):501-7. doi: 10.1097/01.AUD.0000100204.08771.3D.
citation: Starcke K, Mayr J, von Georgi R. Emotion Modulation through Music after Sadness Induction-The Iso Principle in a Controlled Experimental Study. Int J Environ Res Public Health. 2021 Nov 26;18(23):12486. doi: 10.3390/ijerph182312486.
citation: Vernon D, Peryer G, Louch J, Shaw M. Tracking EEG changes in response to alpha and beta binaural beats. Int J Psychophysiol. 2014 Jul;93(1):134-9. doi: 10.1016/j.ijpsycho.2012.10.008. Epub 2012 Oct 17.