Residual Inhibition of 40 Hz Burst Sound in Tinnitus Patients

NCT ID: NCT06646302

Last Updated: 2025-09-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 265 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-10-28
• Study Completion Date: 2025-07-18

Brief Summary

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.

Detailed 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.

Conditions

Tinnitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Personalized 40 Hz Broadband Stimulation

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.

Group Type: EXPERIMENTAL

Personalized 40 Hz Broadband Stimulation

Intervention Type: OTHER

Broadband acoustic stimulus (125 Hz-12 kHz) amplitude-modulated at 40 Hz with a 50% duty cycle. A polynomial regression and FFT-based algorithm applies individualized frequency weighting, combining population data (70%) and patient-specific responses (30%). Delivered for 60 seconds at 10 dB above the individual minimum masking level (MML).

40 Hz Pure Tone Stimulation

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

Group Type: EXPERIMENTAL

40 Hz Pure Tone Stimulation

Intervention Type: OTHER

Pure tone stimulus at the optimized frequency (matched to tinnitus characteristics or high-frequency carrier), amplitude-modulated at 40 Hz with a 50% duty cycle. Delivered for 60 seconds at 10 dB above MML.

Continuous Broadband Noise

Participants receive continuous broadband noise stimulation without 40 Hz modulation.

Group Type: ACTIVE_COMPARATOR

Continuous Broadband Noise

Intervention Type: OTHER

Continuous broadband noise spanning 125 Hz-12 kHz without 40 Hz modulation. Delivered for 60 seconds at 10 dB above MML as an active control condition.

Interventions

Personalized 40 Hz Broadband Stimulation

Broadband acoustic stimulus (125 Hz-12 kHz) amplitude-modulated at 40 Hz with a 50% duty cycle. A polynomial regression and FFT-based algorithm applies individualized frequency weighting, combining population data (70%) and patient-specific responses (30%). Delivered for 60 seconds at 10 dB above the individual minimum masking level (MML).

Intervention Type: OTHER

40 Hz Pure Tone Stimulation

Pure tone stimulus at the optimized frequency (matched to tinnitus characteristics or high-frequency carrier), amplitude-modulated at 40 Hz with a 50% duty cycle. Delivered for 60 seconds at 10 dB above MML.

Intervention Type: OTHER

Continuous Broadband Noise

Continuous broadband noise spanning 125 Hz-12 kHz without 40 Hz modulation. Delivered for 60 seconds at 10 dB above MML as an active control condition.

Intervention Type: OTHER

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eye & ENT Hospital of Fudan University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Huawei Li, PhD

Role: PRINCIPAL_INVESTIGATOR

Eye and ENT Hospital of Fudan University

Locations

Eye & ENT Hospital of Fudan University

Shanghai, Shanghai Municipality, China

Countries

China

Other Identifiers

2024087

Identifier Type: -

Identifier Source: org_study_id