Residual Inhibition of 40 Hz Burst Sound in Tinnitus Patients

Eye & ENT Hospital of Fudan University

Status: Completed

Conditions: Tinnitus

Treatments: Other: 40 Hz Pure Tone Stimulation; Other: Continuous Broadband Noise; Other: Personalized 40 Hz Broadband Stimulation

Study type: Interventional

Funder types: Other

Identifiers

NCT06646302

2024087

Details and patient eligibility

About

Tinnitus affects 10-15% of adults and is frequently associated with impaired quality of life, anxiety, and sleep disturbance. Conventional sound therapies based on continuous masking provide inconsistent and short-lived relief, and the neural mechanisms underlying residual inhibition (RI) remain unclear.

This study aims to determine whether 40 Hz burst stimulation with high-frequency carriers can achieve longer-lasting RI than continuous sound, and to explore its underlying neural mechanisms using EEG.

Full description

Residual inhibition (RI) refers to the temporary reduction or disappearance of tinnitus following sound stimulation and provides an important clue for identifying patients who may benefit from acoustic therapy. However, the effects of different sound stimulation strategies on RI remain poorly understood.

This study evaluates whether 40 Hz burst-modulated sound achieves stronger and longer RI compared with conventional continuous stimulation. The trial follows a four-phase design:

Phase 1: Exploratory testing of burst versus continuous tones at different frequencies.

Phase 2: Large-scale validation in 265 patients. Phase 3: Development of a personalized stimulation protocol using adaptive spectral optimization.

Phase 4: EEG investigation of neural mechanisms, focusing on gamma oscillations and functional connectivity changes.

The primary outcomes are the strength and duration of tinnitus suppression. Secondary outcomes include EEG markers such as γ-band power spectral density and phase-locking value.

By combining behavioral and neurophysiological measures, this study aims to establish 40 Hz burst stimulation as a novel rhythm-based sound therapy and to provide mechanistic insights that may enable more effective, personalized tinnitus management.

Enrollment: 265 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Diagnosed with subjective tinnitus;
2. Chronic tinnitus: tinnitus course ≥ 1 month;
3. Normal middle ear function;
4. The average hearing threshold (defined as mean of 0.5, 1, 2, and 4 kHz) of the unaffected ear < 60 dB;
5. Tinnitus can be heard under normal circumstances.
6. Subjects are able to understand the purpose of the study, volunteer to participate and cooperate with the instructors to complete the experiment, and be willing to sign the informed consent.

Exclusion criteria

1. Acute phase tinnitus;
2. Fluctuating tinnitus loudness;
3. Severe psychiatric disorders;
4. Inability to complete tinnitus testing;
5. Fluctuating or retrocochlear hearing loss;
6. Conductive hearing loss;
7. Currently participating in other research projects that may affect tinnitus;
8. Subjects who are not considered suitable for this clinical trial by the researchers.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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265 participants in 3 patient groups

Personalized 40 Hz Broadband Stimulation

Experimental group

Description:

Participants receive personalized broadband acoustic stimulation modulated at 40 Hz. An adaptive equalization algorithm, based on individual and population residual inhibition (RI) responses, is used to weight frequency components across 125 Hz-12 kHz.

Treatment:

Other: Personalized 40 Hz Broadband Stimulation

40 Hz Pure Tone Stimulation

Experimental group

Description:

Participants receive pure tone stimulation at the individually optimized carrier frequency identified in earlier phases, amplitude-modulated at 40 Hz.

Treatment:

Other: 40 Hz Pure Tone Stimulation

Continuous Broadband Noise

Active Comparator group

Description:

Participants receive continuous broadband noise stimulation without 40 Hz modulation.

Treatment:

Other: Continuous Broadband Noise